Researchers from the Wellcome Trust Sanger Institute in the U.K. and their collaborators have developed what could potentially be a tabula rasa, or clean slate, for stem cells, which could allow any type of cells to grow and develop. This breakthrough study is published today in the journal Nature, and it shows how researchers, for the first time, created what’s known as Expanded Potential Stem Cells (EPSCs) in mice.
Prior to this breakthrough, stem cell lines existed in two basic types — embryonic stem cells (ES) and induced pluripotent stem cells (iPS). In theory, both stem cell lines can grow to a good number of cell types, and previous research has shown them to be the most effective in doing so. However, ES and iPS have limitations: they aren’t capable of growing into every type of cell, as they’re already limited to only particular cell lines right at the onset. On the other hand, EPSCs are able to form whatever type of cell because they possess features similar to that of the very first cells of their source organism’s embryo. In the case of this study, it was mice. The team is confident, however, that they can develop similar EPSCs from humans as well as other mammals.
To develop the mice EPSCs, the researchers cultured mice cells from their earliest stage of development — i.e., when the fertilized egg has divided into only 4 to 8 cells, each still able to grow into any cell type. In contrast, ES cells are usually taken from around the 100-cell stage in development. Additionally, the researchers developed mouse ES and iPS cells into this new condition and grow EPSCs from them. In short, they were able to turn back the development clock to the earliest type of cell.
Recharging Regenerative Medicine
Already, scientists have been able to achieve quite a lot using available ES and iPS cells. They’re now able to turn skin cells into motor neurons, treat baldness, and even slow aging in mice using stem cells. Indeed, the potential of stem cells in regenerative medicine is currently unprecedented. The new study’s EPSCs can push even further. Accordingly, these EPSCs are the first stem cells able to produce all three types of blastocyst stem cells — differentiated cells from a fertilized egg — which expands their potential for development.
“This is a fantastic achievement, by working with the very earliest cells, this study has created stem cell lines that can form both embryonic and all the extra-embryonic cells. The methods and insights from this study in mice could be used to help establish cultures of similar stem cells from other mammalian species, including those where no ES or iPS cell lines are available yet,” study co-author Hiro Nakauchi of Stanford University explained in a press release.
“The research also has great implications for human regenerative medicine as stem cells with improved development potential open up new opportunities. Further research in this area is vital, so that we can properly explore the potential of these cells,” he added.
Scientists have developed healthy offspring from altered male mice that were once genetically infertile, resulting in a new tool to manage human infertility. The X and Y chromosomes determine sex – with chromosomes (XY) signifying male, and two X chromosomes (XX) signifying female. However, about 1 in 500 boys are born with one extra chromosome. Whether it’s an X or a Y the presence of a third chromosome can cause infertility by disrupting the formation of mature sperm.
Scientists at the Francis Crick Institute have now discovered a technique for removing extra sex chromosomes in developed stem cells and producing fertile offspring. If they can transfer their findings and this technique for application in humans, those with either Double Y syndrome (XYY) or Klinefelter syndrome (XXY) that now experience male chromosomal infertility might one day be able to have children via assisted reproduction.
“Our approach allowed us to create offspring from sterile XXY and XYY mice,” lead author and Francis Crick Institute scientist Takayuki Hirota said in a press release. “It would be interesting to see whether the same approach could one day be used as a fertility treatment for men with three sex chromosomes.”
A Promising Technique
To accomplish this research, the team removed small sections of ear tissue from mice with both XXY and XYY chromosomal anomalies and cultured it. They next collected fibroblasts, which are connective tissue cells, and turned them into stem cells. During the transformation, the researchers noted that some of the cells had dropped the extra sex chromosome. Following this, they used a method developed in the past to guide the stem cells with specific chemical signals into becoming potential sperm cells. Once these cells were injected into mouse testes, they developed into mature sperm. These mature sperm were found to be viable, and so the researchers harvested and used them in assisted reproduction cycles to create fertile, healthy offspring.
The team has also conducted one preliminary experiment using men with Klinefelter syndrome. In that experiment, the researchers followed the first part of the same process and discovered that stem cells produced from the fibroblasts of these men also shed the extraneous sex chromosome. However, this was an early stage experiment, and extensive research remains before the technique will ever be viable for use in humans.
“There is currently no way to make mature sperm outside of the body. In our mouse experiments we have to inject cells that have the potential to become sperm back into the testes to help them finish developing. But we found that this caused tumors in some of the mouse recipients,” senior author and Group Leader at the Francis Crick Institute James Turner explained in the press release. “So reducing the risk of tumor formation or discovering a way to produce mature sperm in a test tube will have to be developed before we can even consider this in humans.”
During their study, which has been published in Nature, the researchers noticed that stem cells found in hair follicles undergo a different metabolic process than normal skin cells. After turning glucose into a molecule known as pyruvate, these hair follicle cells then do one of two things: send the pyruvate to the cell’s mitochondria to be used as energy or convert it into another metabolite known as lactate.
Based on these findings, the researchers decided to see if inactive hair follicles behaved differently depending on the path of the pyruvate.
To that end, the UCLA team compared mice that had been genetically engineered so that they wouldn’t produce lactate with mice that had been engineered to produce more lactate than normal. Obstructing lactate production stopped the stem cells in the follicles from being activated, while more hair growth was observed on the animals who were producing more of the metabolite.
“No one knew that increasing or decreasing the lactate would have an effect on hair follicle stem cells,” co-lead on the study and professor of molecular, cell, and developmental biology William Lowry explained in a UCLA press release. “Once we saw how altering lactate production in the mice influenced hair growth, it led us to look for potential drugs that could be applied to the skin and have the same effect.”
Potential for Growth
Based on their study, the researchers were able to discover two different drugs that could potentially help humans jumpstart the stem cells in their hair follicles to increase lactate production.
The first is called RCGD423, and it works by establishing a JAK/STAT signalling pathway between the exterior of a cell and its nucleus. This puts the stems cells in an active state and contributes to lactate production, encouraging hair growth.
The other drug, UK5099, takes the opposite approach. It stops pyruvate from being converted into energy by the cells’ mitochondria, which leaves the molecules with no choice but to take the alternate path of creating lactate, which, in turn, promotes hair growth.
Both of the drugs have yet to be tested on humans, but hopes are high that if tests are successful, they could provide relief for the estimated 56 million people in the U.S. alone suffering from a range of conditions that affect normal hair growth and retention, including alopecia, hormone imbalances, stress-related hair loss, and even old age.
However, as undoubtedly pleased as many of those people would be to stimulate their hair growth, the potential relevance of this research stretches far beyond hair loss. The new knowledge gained regarding stem cells, specifically their relation to the metabolism of the human body, provides a very promising basis for future study in other realms.
“I think we’ve only just begun to understand the critical role metabolism plays in hair growth and stem cells in general,” noted Aimee Flores, first author of the study and a predoctoral trainee in Lowry’s lab. “I’m looking forward to the potential application of these new findings for hair loss and beyond.”
Old hearts may find new life, according to a new study, which shows that stem cells taken from younger hearts can be used to reverse the aging process. This could potentially cause older hearts to act and perform like younger ones.
The study, conducted by the Cedars-Sinai Heart Institute and published by the European Heart Journal, set out to observe the effects of cardiac stem cells on various aspects of the heart, including its function and structure. Prior applications of Cardiosphere-derived cells (CDC) resulted in positive effects, but this was the first time its effects in the aging process were tested. This is different from the tests performed last month at the Albert Einstein College of Medicine, where the hypothalamus region of the brain was discovered to be a key part of aging in mice.
Cedars-Sinai researchers instead took CDC cells from newborn mice and injected it into the hearts of older mice, while another group of older mice were injected with saline. Blood, echocardiographic, haemodynamic and treadmill stress tests were performed on all mice after injections, with the older groups tested 1 month later.
The mice given the Cardiosphere-derived cells saw a number of benefits compared to their saline counterparts. They had improved heart functionality, were able to exercise 20 percent longer, regrew hair at a faster rate, and had longer heart cell telomeres. This is important because telomeres are compounds found at the ends of chromosomes whose shortening is directly correlated to the aging process.
“The way the cells work to reverse aging is fascinating,” said Cedars-Sinai Heart Institute Director and Lead Researcher Eduardo Marbán, MD, PhD. “They secrete tiny vesicles that are chock-full of signaling molecules such as RNA and proteins. The vesicles from young cells appear to contain all the needed instructions to turn back the clock.”
The World Health Organization reports that more than 422 million people worldwide are living with diabetes, a condition that can take two forms. In the first, the body’s immune system attacks cells in the pancreas, preventing the organ from producing enough insulin [type 1 diabetes (T1D)]. In the second, the body doesn’t know how to use the insulin that is produced [type 2 diabetes (TD2)].
T1D accounts for roughly 10 percent of diabetes cases, and unlike T2D, which can often be reversed through lifestyle changes such as weight loss or increased exercise, scientists have yet to figure out how to prevent or cure T1D.
Right now, T1D is best managed by balancing insulin doses, but this method can be problematic in high-risk cases, taking time to act. Moreover, patients with hypoglycemia (low glucose) unawareness may not notice when their blood sugar drops dangerously low. Thankfully, researchers all over the world are hard at worklooking for a cure that will free T1D patients from their dependence on insulin injections and from risky situations when their levels drop low.
Now, one group may have found such a cure.
Just last week, California-based company ViaCyte began trials involving two T1D patients who were implanted with the company’s PEC-Direct device.
Each of these credit card-sized implants carries cells built from stem cells. These cells are designed to mature inside the human body into the specialized pancreas cells the immune system destroys in those with T1D. The implant is placed just below the skin and releases insulin whenever necessary.
“Patients with high-risk type 1 diabetes complications, such as hypoglycemia unawareness, are at constant risk of life-threatening low blood glucose,” clinical trial investigator Jeremy Pettus from University of California, San Diego, said in a ViaCyte press release. “The PEC-Direct islet cell replacement therapy is designed to help patients with the most urgent medical need.”
“There are limited treatment options for patients with high-risk type 1 diabetes to manage life-threatening hypoglycemic episodes,” added ViaCyte president and CEO Paul Laikind. “We believe that the PEC-Direct product candidate has the potential to transform the lives of these patients.”
Truly, freeing T1D patients from the need for constant insulin shots hasn’t been an easy task. Researchers in Finland have been looking into it for 25 years and only recently did they manage to develop a vaccine for type 1 diabetes — that breakthrough will go to clinical trials by 2018. ViaCyte’s device is another promising discovery.
Prior to last week’s clinical trial, PEC-Direct implants using smaller amounts of stem cells were tested in 19 diabetes patients. Although these did mature into the desired islet cells, the limited number wasn’t designed to treat the condition. The PEC-Direct implants received by the two patients last week contain more cells. The hope is that three months from now, when the cells have matured, they’ll be able to take the place of injections by releasing insulin automatically when needed.
If it does work, the only thing T1D patients will have to do is take immunosuppressant drugs to make sure their bodies don’t reject the new cells. That’s a small price to pay to be freed of daily injections. As James Shapiro at the University of Alberta, Canada, told New Scientist, “A limitless source of human insulin-producing cells would be a major step forward on the journey to a potential cure for diabetes.”
Editor’s Note: This article has been updated. A previous version implied that individuals should take insulin when blood sugar levels are low. This has been updated to note that individuals need insulin when sugar levels are high.
Of the many diseases that have plagued humanity, HIV is proving to be one of the trickiest to cure. The virus’ ability to remain hidden in latent reservoirs makes eliminating it particularly challenging, which is why Chinese researchers decided to test a different approach. Instead of developing a drug to fight HIV, they’re working on a way to make cells immune to the virus.
Previous studies have shown that this mutation of CCR5 can prevent HIV from entering cells, but only a small percentage of people have it naturally. Using CRISPR/Cas9, the researchers edited human fetal liver hematopoietic stem/progenitor cells (HSPCs), which were then engrafted into mice. Their research showed that this targeted approach of editing CCR5 was effective at making T-cells more resistant to HIV.
While this study isn’t the first to use edited stem cells to develop HIV-resistance in immune cells, it is the first example of using CRISPR to edit CCR5. “One of the advantages of CRISPR is its high efficiency on difficult to transfect cells,” Cheng and Deng told The Scientist. Using the remarkable method, they achieved a 21 to 28 percent efficiency in editing CCR5.
As for this CCR5 study, Kamel Khalili from Temple University told The Scientist that expectation should remain in check: “[It] may not be a complete cure because the virus itself is not eliminated and may shift to using the CCR4 or another receptor to spread.” However, he did add, “CCR5 seems to be the one Achilles heel of HIV. There may be some other targets, but for now, it’s the best target.”
Researchers at the Albert Einstein College of Medicine in New York have successfully tested a new procedure on mice that could help keep age-related diseases, and even aging itself, at bay. Reporting their findings in the journal Nature, the researchers discovered the crucial role the hypothalamus —the region of the brain responsible for the body’s hormonal and metabolic processes— plays in aging.
“Our research shows that the number of hypothalamic neural stem cells naturally declines over the life of the animal, and this decline accelerates aging,” led researcher Dongsheng Cai said in a press release. They found, however, that the process isn’t irreversible.
In order to figure out if the disappearance of stem cells was caused by (or due to) aging, they injected mice with a toxin that killed 70 percent of their neural stem cells. “This disruption greatly accelerated aging compared with control mice, and those animals with disrupted stem cells died earlier than normal,” Cai explained.
In a second experiment, the researchers implanted stem cells ready to become fresh neurons into the brains of older mice. This extended the life of the mice by 10 to 15 percent, and kept them physically and mentally fit for several months.
Getting a Handle on Aging
Previously, other researchers have hinted at the role the hypothalamus has in aging — though it has never before been pinpointed quite so clearly. Cai’s team seems to have provided the missing link, which could significantly pushed anti-aging research forward. “It is a tour de force,” David Sinclair at Harvard Medical School told The Guardian. “It’s a breakthrough. The brain controls how long we live.”
For Cai’s research, the next step is to test the procedure on humans, and the team wants to begin clinical trials soon. However, that may be a ways off yet. “Of course humans are more complex,” Cai said, also speaking to The Guardian. “However, if the mechanism is fundamental, you might expect to see effects when an intervention is based on it.”
Nothing is as certain as death. Yet humans have come up with ways to push it further and further. The heart stops beating? Do CPR. The lungs fail? Use a mechanical ventilator. These techniques have saved the lives of millions. There is a point of no return, however: when the brain dies.
One company, Philadelphia-based Bioquark Inc., thinks it may be possible to push back on even that last step. Bioquark plans to launch a study to use stem cells and a slew of other therapies to bring a glimmer of life back to the dead brains of newly deceased patients.
The idea led to hundreds of chilling headlines and has met serious backlash from scientists and ethicists alike. While Bioquark’s proposed study may trigger ethical and practical concerns, experts do say advances in stem cell research and medical technologies mean someday brain injury could be reversible. Maybe (and that’s a big maybe) brain death won’t be the end of life.
“I agree stem cell technology in the neurosciences has tremendous potential, but we have to study it in a way that makes sense,” said Dr. Diana Greene-Chandos, assistant professor of neurosurgery and neurology at Ohio State University Wexner Medical Center. What doesn’t make sense, she says, is to apply stem cell research in complex human brains — very damaged ones — before animal studies have gotten far enough.
That’s why Bioquark’s proposed study, slated to take place in South America sometime this year, has caused such uproar in the science community. The team plans to administer therapies to 20 brain-dead subjects with the hope of stirring up electrical activity in the brain. The idea is to deliver stem cells to the brain and coax them to grow into new brain cells, or neurons, with the help of a nurturing peptide cocktail, electrical nerve stimulation, and laser therapy.
“We are employing this [combined] approach, using tools that by themselves have been employed extensively, but never in such an integrated process,” said Bioquark CEO Ira Pastor.
One critique is that such a study could give false hope to families who may have a poor understanding of the severity and irreversibility of brain death, and confuse it with coma or vegetative state. “There are a lot of gray areas in medicine. And we should all keep an open mind. But we need to make sure we are not misguiding our patients,” said Dr. Neha Dangayach, attending physician in the neurosurgical intensive care Unit at New York’s Mount Sinai Hospital.
Pastor’s response to the criticism? The public is catching up to the idea of brain death. He’s also clarified that full resurrection is not the company’s intended goal — at least not yet. “We are not claiming the ability to erase death. We are working on a very small window, a gray zone between reversible coma and death,” he said.
Ethics aside, critics say there are practical problems with the plan. There is insufficient evidence behind Bioquark’s approach, they argue, and the way the study is planned does not sound realistic.
When the brain dies, inflammation and swelling run amok, the connections between neurons disintegrate, arteries collapse, and blood flow shuts down. “Once someone is brain-dead, you can keep them on the ventilator but it’s very hard to keep the organs from shutting down and the heart beating for more than a few days,” said neurologist Richard Senelick. “Nature is going to run its course.”
So, many scientists say Bioquark’s study may be a quixotic quest — on par with cryogenic brain preservation and head transplants. They may sound good in theory but are so impractical that they have little chance of success. Nevertheless, experts agree the quest does raise serious questions that deserve answers. Just what would it take to save a brain? Perhaps resurrecting dead brains is not in the realm of possibility…but what is?
Brain Death and the Cell ‘Suicide Switch’
There is an immense reward in pursuing brain regeneration. If it pans out, it could potentially save the lives of those who are injured in an accident or, more commonly, suffer extreme brain damage following a cardiac arrest or stroke. Every year in the United States, about 350,000 people experience an out-of-hospital cardiac arrest, according to the American Heart Association. Only about 10 percent survive with good neurologic function. Another 130,000 people die of stroke annually.
To appreciate the challenge of saving the brain, first look at what it takes to kill it. It was long thought that death occurs when the heart stops. Now we know that death actually happens in the brain—and not in one single moment, but several steps. A patient lying in a coma in an intensive care unit may appear peaceful, but findings from biochemical studies paint a much different scene in his brain: fireworks at the cellular level.
When neurons encounter a traumatic event, like lack of blood flow after cardiac arrest, they go into a frenzy. Some cells die during the initial blackout. Others struggle to survive in the complex cascade of secondary injury mechanisms, triggered by the stress of being deprived of oxygen. Neurotransmitters spill out of neurons in high concentrations. Free radicals pile up, burning holes in brain cell membranes. The pierced cells respond to the attack by producing more inflammation, damaging other cells.
Eventually, the stress response triggers apoptosis, or the process of programmed cell death. In other words, the cell’s “suicide switch” gets turned on. The cells die one by one until the brain ceases to function.
That’s brain death: the complete and irreversible loss of function of the brain. Doctors determine brain death by checking whether the patient’s pupils react to light, whether he responds to pain, and if his body tries to breathe or has retained any other vital function of the brainstem, the part most resilient to injury.
“We have strict tests, because it’s a very serious question—the question of distinguishing life from death,” Dangayach said.
For brain damage at a much smaller scale, however, the situation could be manageable. Cutting-edge therapies are focused on this possibility.
More Neurons in a Pill?
Stem cells have brought an exciting potential opportunity to the grim area of treating brain injury. Currently, there’s no FDA-approved stem cell-based therapy for brain problems, and experts suggest staying away from any clinic that offers such therapies. But that doesn’t stop researchers from being excited about the possibilities. Unlike in other parts of the body, cells lost in the brain are gone forever. Could stem cells replace them?
“That’s a reasonable thing to ask,” neurologist Dr. Ariane Lewis of New York University said. Lewis is a strong critic of Bioquark’s approach, saying that the study “borders on quackery,” but she thinks stem cell research is promising for stroke recovery. “We have little evidence right now, and this is not a commonly employed therapy, but it’s a research question.”
Two regions in the adult brain contain stem cells that can give rise to new neurons, suggesting the brain has a built-in capacity to repair itself. Some of these cells can migrate long distances and reach the injury site.
In some injuries, the brain produces biological factors that stimulate stem cells. Researchers are working to identify those factors — with the aim of someday translating the findings into new drugs to boost a patient’s own stem cells.
“If we can identify factors that stimulate these cells we could directly repair [the brain],” said Dr. Steven Kernie, chief of pediatric critical care medicine at New York Presbyterian Hospital, who is working on this research.
Other teams have been working on turning different types of brain cells into neurons. A team at Penn State University developed a cocktail of molecules that can convert glial cells, a type of brain cell, into functioning neurons in mice. The cocktail of molecules could be packaged into drug pills, the researchers said, perhaps one day taken by patients to regenerate neurons.
Another option: transplant new neurons into the brain. In a 2016 study, scientists successfully transplanted young neurons into damaged brains of mice. A real-life injury in the human brain is a much messier situation than a clear-cut lesion made in the lab. But eventually, such advances may translate into techniques to repair stroke damage.
For diseases like Parkinson’s, in which a particular population of neurons is lost—as opposed to widespread indiscriminate damage — there have been several clinical trials with many more slated. Scientists in Australia are using brain cells of pigs as a substitute for lost neurons. Later this year, a Chinese clinical trial will implant young neurons derived from human embryonic stem cells into brains of Parkinson’s patients. And five more groups are planning similar trials over the next two years, Nature reported.
Approaches taken in Parkinson’s trials may be the most biologically plausible, Kernie said. If these trials are successful, they may pave the way for more widespread application of stem cells for treating brain diseases. “It’s not proven yet that it will work, but it’s something that’s on the horizon.”
“These Scientists Have a Plan To Cheat Death. Will It Work?” was originally published by NBC Universal Media, LLC on June 29, 2017 by Bahar Gholipour. Copyright 2017 NBC Universal Media, LLC. All rights reserved.
Scientists at Monash University in Australia have found another piece of the lab-grown organ puzzle: the team has discovered that a protein called Meox1 is pivotal in promoting the growth of muscles. They came across the protein while studying zebrafish, which are ideal candidates for the research due to their rapid rate of growth and biological similarities with humans. We share 70 percent of our DNA with the species, and they have many of the same internal organs that we do.
Meox1 directs muscle growth by selecting the relevant stem cells for producing the specific tissue (as opposed to the growth being caused by stem cells dividing at random).
Lead researcher on the study, Peter Currie, said in a statement “prior to our work in this field, we didn’t even know that these growth-specific stem cells existed or how they were used […] Just knowing that they exist leads us to the possibility of orchestrating them, controlling them, or reactivating them to regrow damaged tissue.”
Stem Cell Saviors
This research is pivotal because it doesn’t just show is what the stem cells do — it shows us how. Researchers have known for quite some time that stem cells produce living tissue in the body, but up until this point we haven’t understood the mechanism behind how they do it.
Accruing this piece of knowledge means we have crossed, as the team called it, “one of last frontiers of developmental biology.” It’s also a significant step towards being able to encourage stem cell growth in lab conditions.
When the process is fully developed, the ability to grow organs in laboratories will save thousands of lives. It will allow us to create tailored organs rather than patients waiting for a matching donor to be found. Estimates from the American Transplant Foundation indicate that a new name is added to the organ donor list every 10 minutes, and that 22 people a day die while waiting for a transplant each day.
Human cloning may endure as one of the go-to science fiction tropes, but in reality we may be much closer to achieving it than our fictional heroes might imply. At least in terms of the science required. On of the most prominent hurdles facing us may have less to do with the process and more to do with its potential consequences, and our collective struggle to reconcile the ethics involved. That being said, while science has come a long way in the last century when it comes to cloning a menagerie of animals, cloning humans and other primates has actually proven to be incredibly difficult. While we might not be on the brink of cloning entire human beings, we’re already capable of cloning human cells — the question is, should we be?
The astoundingly complex concept of cloning boils down to a fairly simple (in theory, at least) practice: you need two cells from the same animal — one of which is an egg cell from which you’ve removed the DNA. You take the DNA from the other somatic cell and put it inside the devoid-of-DNA egg cell. Whatever that egg cell goes on to produce for offspring will be genetically identical to the parent cell. While human reproduction is the result of the joining of two cells (one from each parent, each with their own DNA) the cellular photocopy technique does occur in nature. Bacteria reproduce through binary fission: each time it divides, its DNA is divided too so that each new bacterium is genetically identical to its predecessor. Except sometimes mutations occur in this process — and in fact, that can be by design and function as a survival mechanism. Such mutations allow bacteria to, for example, become resistant to antibiotics bent on destroying them. On the other hand, some mutations are fatal to an organism or preclude them coming into existence at all. And while it might seem like the picking-and-choosing that’s inherent to cloning could sidestep these potential genetic hiccups, scientists have found that’s not necessarily the case.
Image Credit: Pixabay
What The Experts Say
While Dolly the sheep might be the most famous mammal science has ever cloned, she’s by no means the only one: scientists have cloned mice, cats, and several types of livestock in addition to sheep. The cloning of cows has, in recent years, provided a great deal of knowledge to scientists about why the process doesn’t work: everything from implantation failure to those aforementioned mutations that render offspring unable to survive. Harris Lewin, professor in the UC Davis Department of Evolution and Ecology, and his team published their findings on the impact cloning has on gene expression in the journal Proceedings of the National Academy of Sciences back in 2016. In the study’s press release Lewin noted that the findings were certainly invaluable to refining cloning techniques in mammals, but that their discoveries “also reinforce the need for a strict ban on human cloning for any purposes.”
The creation of entire mammals via reproductive cloning has proven a difficult process both practically and ethnically, as legal scholar and ethicist Hank Greely of Stanford University explained to Business Insider in 2016:
“I think no one realized how hard cloning would be in some species though relatively easy in others. Cats: easy; dogs: hard; mice: easy; rats: hard; humans and other primates: very hard.”
The cloning of human cells, however, may be a far more immediate application for humans. Researchers call it “therapeutic” cloning, and differentiate it from traditional cloning that has reproductive intent. In 2014, researchers created human stem cells through the same cloning technique that generated Dolly the sheep. Because stem cells can differentiate to become any kind of cell in the body, they could be utilized for a wide variety of purposes when it comes to treating diseases — particularly genetic diseases, or diseases where a patient would require a transplant from an often elusive perfect match donor. This potential application is already well underway: earlier this year a woman in Japan suffering from age-related macular degeneration was treated with induced pluripotent stem (iPS) cells created from her own skin cells, which were then implanted into her retinas and stopped her vision from degenerating further.
We asked the Futurism community to predict when they think we’ll be able to successfully clone a full human, and the majority of those who responded agree that it feels like we’re getting close: nearly 30 percent predicted we’ll clone our first human by the 2020s. “We have replaced, and replicated almost every biology on earth,” said reader Alicja Laskowska, “[the] next step is for cures and to do that you need clean DNA, and there’s your start.”
This trial was originally intended to go forward in 2016 in India, but regulators shut it down. Assuming this plan will be substantially similar, it will enroll 20 patients who will undergo various treatments. The stem cell injection will come first, with the stem cells isolated from that patient’s own blood or fat. Next, the protein blend gets injected directly into the spinal cord, which is intended to foster growth of new neurons. The laser therapy and nerve stimulation follow for 15 days, with the aim of prompting the neurons to make connections. Meanwhile, the researchers will monitor both behavior and EEGs for any signs of the treatment causing any changes.
While there is some basis in science for each step in the process, the entire regimen is under major scrutiny. The electrical stimulation of the median nerve has been tested, but most evidence exists in the form of case studies. Dr. Ed Cooper has described dozens of these cases, and indicates that the technique can have some limited success in some patients in comas. However, comas and brain death are very different, and Bioquark’s process raises more questions for most researchers than it answers.
One issue researchers are raising about this study is informed consent. How can participants in the trial consent, and how should researchers complete their trial paperwork – given that the participants are legally dead —and how can brain death be conclusively confirmed, anyway? What would happen if any brain activity did return, and what would the patient’s mental state be? Could anything beyond extreme brain damage even be possible?
As reported by Stat News, In 2016, neurologist Dr. Ariane Lewis and bioethicist Arthur Caplan wrote in Critical Care that the trial is “dubious,” “has no scientific foundation,” and suffers from an “at best, ethically questionable, and at worst, outright unethical nature.” According to Stat News, despite his earlier work with electrical stimulation of the median nerve, Dr. Cooper also doubts Bioquark’s method, and feels “there is no way this technique could work on someone who is brain-dead. The technique, he said, relies on there being a functional brain stem — one of the structures that most motor neurons go through before connecting with the cortex proper. If there’s no functional brain stem, then it can’t work.”
Pediatric surgeon Charles Cox, who is not involved in Bioquark’s work, agrees with Cooper, commenting to Stat News on Bioquark’s full protocol, “it’s not the absolute craziest thing I’ve ever heard, but I think the probability of that working is next to zero. I think [someone reviving] would technically be a miracle.”
Pastor remains optimistic about Bioquark’s protocol. “I give us a pretty good chance,” he said. “I just think it’s a matter of putting it all together and getting the right people and the right minds on it.”
In two separate studies, researchers have successfully created blood stem cells in a laboratory setting for the first time. These types of cells are found in bone marrow and can be depleted by diseases like leukemia and even by the treatments for those diseases, such as chemotherapy.
George Daley, Dean of the Faculty of Medicine at Harvard, and his team started with pluripotent stem cells, which can give rise to just about any type cell in our anatomy. By looking at what proteins controlled the genes in bone marrow cells, they were able to isolate several that were essential to cell differentiation (the process by which stem cells become a specific kind of cell). They then applied them to the pluripotent cells in order to encourage them to turn into the cells found in bone marrow.
Another team lead by Raphael Lis, Instructor in Medicine at Weill Cornell Medical College, took cells from the lungs of animals, and found four factors that encourage the lung stem cells to make blood stem cells. In their report they “demonstrate a tractable approach for fully reprogramming adult mouse endothelial cells to haematopoietic stem cells.” The next steps for Lis are to streamline the “conceived […] reproducible approach to manufacture engraftable durable blood cells”, so they can be produced on a larger scale.
No Donors Required
Carolina Guibentif of the University of Cambridge Institute for Medical Research (who was not part of either study) told New Scientist that “If you can develop [these cells] in the lab in a safe way and in high enough numbers, you wouldn’t be dependent on donors.” That is, after the cells are tested on human subjects; thus far, they’ve only been tested on mice. Because the cells are engineered, they aren’t as good at making blood as their natural counterparts. There’s also always the risk of mutation, which could lead to cancer. The researchers are well aware of this potential, though, and with the additional research required to work out these quirks and kinks, their breakthrough is certainly a hopeful one.
Dr. Joseph Scandura, a senior co-author of the Weill Cornell study, said the engineered cells could one day “fix [a patient’s] disease be it leukemia or sickle cell anemia or HIV.” Recent findings by scientists from the University of Wisconsin-Madison and Cedars-Sinai in Los Angeles have discovered that stem cells can also be a valid form of treatment for many neurological conditions.
In terms of bone marrow, though, there is great need for donors in the United States. In 2016, the American Red Cross issued multiple appeals, which culminated by the end of the year, when statistics indicated that the supply was 37,000 donors less than it needed to be. Bone marrow transplants are also lacking, in part because of how difficult it is to find a match. The chance of a bone marrow transplant from a sibling working is 1 in 4. Between total strangers, the chance of a match is 1 in a million. For patients whose lives depend on a match, the findings of these studies could make those odds look a lot more favorable.
The human body is a melding of different systems designed to function well together. In some cases, however, a mechanism that protects the body can also cause it harm, like with the specialized shield of endothelial cells — called the blood-brain barrier — that keeps toxins in the blood from entering the brain.
Due to a genetic defect, the blood-brain barrier could prevent essential biomolecules needed for normal brain development from passing through. An example is the Allan-Herndon-Dudley syndrome (AHDS), which is a psychomotor disease resulting from a defective gene that controls the influx of thyroid hormones to the brain. This rare but severe disorder is also unique to humans, making it very difficult to develop treatments that could be lab tested on animals.
So, to study this unique disorder, scientists from the University of Wisconsin-Madison and Cedars-Sinai in Los Angeles used the cells of AHDS patients to recreate the patients’ blood-brain barriers via induced pluripotent steam (iPS) cells technology. What they learned using the model gave the researchers some leads on potential therapies for the disease. They published their study in the journal Cell Stem Cell.
Eliminating Barriers, So to Speak
The researchers managed to make a laboratory model for AHDS. “This is the first demonstration of using a patient’s cells to model a blood-brain barrier defect,” senior author, Eric Shusta, explained in a press release. “If we had just the (compromised) neural cells available, we wouldn’t have been able to identify this key characteristic of AHDS.”
Thanks so their innovation, there’s now a framework to develop new treatments that could prevent or mitigate the debilitating effects of AHDS, according to senior author Clive Svendsen from Cedars-Sinai.
Furthermore, the research could also apply to other neurological disorders that may also have roots in a dysfunctional blood-brain barrier, like Alzheimer’s disease and Huntington’s disease. “The significance of this study expands beyond the limits of AHDS research, to the possibility of stem cell modeling the blood-brain barrier component in many other neurological diseases,” said Gad Vatine, lead author for the study, in the press release.
Major strides are being made in the field of regenerative medicine. Developments have been made growing tissue and even organs in labs to help restore normal functionality in patients. Many of these regenerative therapies take advantage of the advancements made in stem cell research. There have already been breakthroughs that could potentially give us the ability to repair nerve damage or even grow entire organs and limbs.
A new initiative is seeking to speed up innovation in this area of medicine. The Wake Forest Institute for Regenerative Medicine (WFIRM) is leading the $20 million initiative to, according to a release from the hospital, “apply advanced manufacturing to regenerative medicine. The goal is to speed up the availability of replacement tissues and organs to patients.”
“We are excited to be at the forefront of this next frontier in regenerative medicine,” says Anthony Atala, M.D., director of WFIRM, who is looking forward to revolutionizing and invigorating this field of medicine. “Just like the invention of the moving assembly line reduced the cost of cars and made them commonplace, the field of regenerative medicine must develop standardized manufacturing processes to successfully make replacement tissues and organs more widely available.”
According to the release, the initiative is focused on two main projects. The first aims to create standardized “bioinks” that can be used in the process of printing tissue and organs. The second project will focus on developing standardized liquids on which the printed cells can grow.
Standardizing materials and practices will lead to better treatments being developed at a quicker pace. On the regulatory side, it will also speed up the approval process so these lifesaving treatments can be used expediently.
Regenerative medicine will open up new possibilities in the medical field. There will be new options for patients in treatment that would have, until very recently, been thought of as only possible in science-fiction.
The key difference between the two is that iPS cells are made from skin cells (called fibroblasts) and EPS cells are made from a combination of skin cells and embryonic stem cells. iPS cells are the hallmark of stem cell research and can be programmed to become any cell in the human body — hence the “pluripotent” part of their name. EPS cells, too, can give rise to any type of cell in the human body, but they can also do something very different — something unprecedented, actually: they can create the tissues needed to nourish and grow an embryo.
“The discovery of EPS cells provides a potential opportunity for developing a universal method to establish stem cells that have extended developmental potency in mammals,” says Jun Wu, one of the study’s authors and senior scientist at the Salk Institute, in the organization’s news release.
Chemicals and Chimeras
When a human — or any mammalian — egg gets fertilized, the cells divide up into two task forces: one set is responsible for creating the embryo, and the other set creates the placenta and other supportive tissues needed for the embryo to survive (called “extra-embryonic tissues”). This happens very early in the reproductive process — so early, in fact, that researchers have had a very hard time recreating it in a lab setting.
By culturing and studying both types of cells in action, researchers would not only be able to understand the mechanism that drives it, but hopefully could shed some light on what happens when things go wrong, like in the case of miscarriage.
The researchers at the Salk Institute managed to form a “chemical cocktail” of four chemicals and a type of growth factor that created a stable environment in which they could culture both types of cells in an immature state. They could then harness the two types of cells for their respective abilities.
What they discovered was that not only were these cells extremely useful for creating chimeras (where two types of animal cells — or human and animal cells — are mixed to form something new), but were also technically capable of creating and sustaining an entire embryo. At least in theory: while they were able to sustain both human and mouse cells, the ethical considerations of creating a human embryo this way have prevented them from attempting it.
That being said, there’s no shortage of applications for this type of stem cell: researchers will be able to use them to model diseases, regenerate tissue, create and trial drug therapies, and study in depth early reproductive processes like implantation. Human-animal chimeras may also help engineer organs for transplant — or, you know, give rise to the next superhero.
The brain is one of the most vital organs in the human body, so damage to the brain from injury or aging can have major impacts on people’s quality of life. Neurological disorders represent some of today’s most devastating medical conditions that are also difficult to treat. Among these is Alzheimer’s disease.
Usually, research involving Alzheimer’s rely on brain cells from mice. Now, neurobiologists from the University of California, Irvine (UCI) have developed a method that could allow the use of human cells instead of animal ones to help understand neurological diseases better.
In their study, which was published in the journal Neuron, the researchers found a way to transform human skin cells into stem cells and program them into microglial cells. The latter make up about 10 to 15 percent of the brain and are involved in the removing dead cells and debris, as well as managing inflammation. Micgrolia are instramental in neural network development and maintenance, explained researcher Mathew Blurton Jones, from UCI’s Department of Neurobiology & Behavior.
“Microglia play an important role in Alzheimer’s and other diseases of the central nervous system. Recent research has revealed that newly discovered Alzheimer’s-risk genes influence microglia behavior,” Jones said in an interview for a UCI press release. “Using these cells, we can understand the biology of these genes and test potential new therapies.”
A Renewable Method
The skin cells had been donated by patients from UCI’s Alzheimer’s Disease Research Center. These were first subjected to a genetic process to convert them into induced pluripotent stem (iPS) cells — adult cells modified to behave as an embryonic stem cell, allowing them to become other kinds of cells. These iPS cells were then exposed to differentiation factors designed to imitate the environment of developing microglia, which transformed them into the brain cells.
“This discovery provides a powerful new approach to better model human disease and develop new therapies,” said UCI MIND associate researcher Wayne Poon in the press release. The researchers, in effect, have developed “a renewable and high-throughput method for understanding the role of inflammation in Alzheimer’s disease using human cells,” according to researcher Edsel Abud in the same source.
In other words, by using human microglia instead of those from mice, the researchers have developed a more accurate tool to study neurological diseases and to develop more targeted treatment approaches. In the case of Alzheimer’s, they studied the genetic and physical interactions between the disease’s pathology and the induced microglia cells. “These translational studies will better inform disease-modulating therapeutic strategies,” Abud added in the press release.
Furthermore, they are now using these induced microglia cells in three-dimensional brain models. The goal is to understand the interaction between microglia and other brain cells, and how these influence the development of Alzheimer’s and other neurological diseases.
The ability to regenerate body parts has always been a fascinating prospect, inspiring characters like Wolverine who can instantly heal themselves and regrow body parts they’ve lost — and now regeneration has inspired scientific research. Many species in the animal kingdom can regenerate: arthropods (like scorpions) can regrow appendages, some annelids (like worms) can regenerate from only a few segments of their body, echinoderms (like starfish) can both self-amputate and re-grow limbs, amphibians (like salamanders and newts) can regenerate a limb in as little as a month, and some reptiles can regenerate their tails.
The aquatic acorn worm, a small coral reef dweller that burrows in the sand and one of the closest invertebrate relations to the human, can regenerate any part of its body that has been cut off, even its nervous system and head. Cutting an acorn worm in half simply results in two complete, indistinguishable specimens within fifteen days. They are also unusually similar in body structure to humans. Researchers wondered: since humans have most of the same genes, shouldn’t we be able to do the same thing?
“I really think we as humans have the potential to regenerate, but something isn’t allowing that to happen,” biology professor Billie Swalla commented in a University of Washington (UW) press release describing his recent work. Swalla is the Director of Friday Harbor Laboratories and part of a research team, along with Shawn Luttrell, that’s focused on the study of regeneration in invertebrates. “I believe humans have these same genes, and if we can figure out how to turn on these genes, we can regenerate.”
Although it may sound like only the most fanciful science fiction, many research scientists believe that the regeneration of human body parts is achievable. We already regenerate skin, pieces of other organs, and nails; we also have many of the necessary genes. “We share thousands of genes with these animals, and we have many, if not all, of the same genes they are using to regenerate their body structures,” says Luttrell. “This could have implications for central nervous system regeneration in humans if we can figure out the mechanism the worms use to regenerate.”
Reverse Engineering Worms
The human roadmap that is contained in our DNA is present in every cell in our bodies, and it should also contain enough information to build or regenerate the body. However, access to that part of the plan is not accessible in humans for some evolutionary reason. One possible reason for this is that regeneration may take too much energy in a large, complex organism like a human. Another could be that our highly developed immune system actually stops the process with responses such as scar formation.
The UW team has been investigating which gene expression patterns take place when regeneration begins in acorn worms. Since regeneration follows precisely the same steps in every worm once it starts, the researchers believe that a “master control” gene may exist. If such a gene is what starts the process, it may be able to trigger regeneration in humans.
They are also attempting to identify which kinds of cells function as the building blocks of regeneration. Stem cells are an obvious possibility, but there may be other types of cells which could be repurposed for regeneration. Eventually, the team hopes to use gene activation or editing to start the process in other animals, including humans.
Ultimately, this would change the face of medicine. Burn victims could regenerate their skin, people would no longer need to wait for organ transplants, and if limbs were lost in an accident, they could be regrown. This technology, if it is possible, is not happening anytime soon. The challenges are complex, and so is the duplication of working human nervous systems, brains, and internal organs that would need to be mastered. Genetically we are in a favorable position, and our progeny may see human regeneration as part of our medical reality in 100 years or so.
Parkinson’s disease is one of the world’s most common neurodegenerative ailments. It causes patients with Parkinson’s to lose dopamine neurons, which are important for the motor control centers of the brain. According to statistics from the Parkinson’s Disease Foundation, there are over 10 million people worldwide who suffer from it, with about 60,000 diagnosed cases in the United States alone.
Researchers from the the Karolinska Institute in Stockholm developed a stem cell-based treatment that doesn’t rely on embryonic or adult stem cells, which are often too difficult to harness and transplant into the brain. Instead, they found a way to reprogram the brain’s astrocytes — support cells for neurons — into dopamine neurons.
“You can directly reprogram a cell that is already inside the brain and change the function in such a way that you can improve neurological symptoms,” senior author Ernest Arenas explained to the Scientific American.
The trick was adding a cocktail of three genes and a small RNA molecule to force astrocytes into becoming dopamine neurons. The treatment was tested on mice whose dopamine neurons in brain were destroyed to simulate Parkinson’s disease. Within five weeks of being injected with this gene cocktail, the mice showed improved and more coordinated movement. These results were published in the journal Nature Biotechnology.
A Novel Approach
While this stem cell approach won’t cure Parkinson’s, it can certainly improve current standard treatments for it. For one, astrocytes are already present in the brains of Parkinson’s patients. Reprogramming these would eliminate the need for donor cells, which run the usual incompatibility risks associated with transplants. Second, the proteins produced in the treatment are involved in normal cellular processes, limiting potential side effects that current drug-based therapies often carry.
“This is like stem cell 2.0. It’s the next-generation approach to stem cell treatments and regenerative medicine,” said James Beck, VP and chief scientific officer for the Parkinson’s Disease Foundation, a nonprofit organization that was not involved with the research.
Still, there’s a long way to go before an actual cure can be developed. “Motor improvement is only half the battle,” Beck said to Scientific American. But winning half the battle is still significant. This new approach, he noted, could ease the management of motor symptoms in potentially millions of Parkinson’s patients. It might also make keeping up with medications simpler for them, potentially reducing the eight or more pills that patients with advanced Parkinson’s often take.
Further research is needed to make sure that this reprogramming method doesn’t change other cells in the brain. Only then would it be ready for human clinical trials. But Beck is hopeful that this study will spur new Parkinson’s treatments down the road. “This is an insight into what the future of Parkinson’s treatment holds,” Beck noted.
Macular degeneration is the leading cause of progressive vision loss with almost 10 million Americans affected by the disease. Currently, there are no known cures for the condition — although stem cells might change that entirely.
Macular degeneration occurs when the central portion, the macula, of the retina is deteriorated. This is where our eyes record images and send them to the brain through the optic nerve. The macula is known for focusing our vision, controlling our ability to read, recognize faces, and see objects clearly.
A Japanese man in his sixties is the world’s first person to receive induced pluripotent stem (iPS) cells donated by a different individual. Rather than tip-toeing around the ethics of embryonic stem cells, scientists were able to remove mature cells from a donor and reprogram them into an embryonic state, which then could be developed into a specific cell-type to treat the disease. Physicians cultivated donated skin cells that were transplanted onto the man’s retina to halt the progression of his age-related macular degeneration.
While the man’s first surgery was a success, the doctors have said they will make no more announcements about his progress until they have completed all five of the planned procedures. While the effectiveness of this technique cannot be evaluated until the fate of the donated cells and the progression of the patient’s macular degeneration have been fully monitored, there is increasing interest in using iPS cells for theraputic purposes.
Sharing Stem Cells
A similar therapy was performed at the Kobe City Medical Center General Hospital in Japan in September 2014, but with a slight difference. In this case, the patient received her own skin cells reprogrammed into retinal cells. As hoped, a year after the surgery her vision had no decline, seemingly halting the macular degeneration. Four more patients in the clinical trial are expected to receive donor cells as well.
The donor-cell procedure, if successful, could help pave the way for the iPS cell bank that Shinya Yamanaka is establishing. An iPS cell bank would allow physicians find the perfect iPS donor per each patient’s biological signatures. Yamanaka is a Nobel-prizewinning scientist at Kyoto University who pioneered the iPS cells.
Yamanaka’s idea of a iPS cell bank has the potential to revolutionize modern medicine. It would provide patients with ready-made cells immediately, giving a widespread population access to more treatment options by lower all-around costs. While the risk of genetic defects or a poor donor match still remains, the new procedure could offer enormous advantages compared to other alternatives.
Macular degeneration affects more than 10 million people in the U.S., and is the most common cause of vision loss. It is caused by the deterioration of the middle of the retina, called the macula. The macula focuses central vision and controls our ability to see objects in fine detail, read, recognize colors and faces, and drive a car. Until now, the disease has been considered incurable.
An octogenarian with the condition is now the first person to receive successful treatment with induced pluripotent stem (iPS) cells. The progression of the woman’s macular degeneration was arrested by new retinal cells made in the lab. Unlike embryonic stem cells, iPS cells can be created from regular adult cells. In this case, the cells used to repair the damaged retina from macular degeneration came from the woman’s skin.
The team at Kobe, Japan’s RIKEN Laboratory for Retinal Regeneration, led by Masayo Takahashi, created iPS cells from the patient’s skin cells. Then, they encouraged them to form cells to patch the retinal pigment epithelium. These cells help nourish and support the retina, allowing it to capture the light the eye needs to see.
Once the cells were transformed, the team used them to make a slither measuring 1 by 3 millimeters. This was the patch they used to replace the diseased tissue removed from the patient’s retina. Their aim was to stop the degeneration and save her sight. The results show that the procedure was technically a success: although her vision did not improve, the degeneration stopped.
A possible concern about this treatment, however, is that creating new tissues from stem cells could cause genetic mutations, which might in turn lead to cancer. While more research in this area — and its possible applications — is needed, in the case of the patient at RIKEN, there have been no signs of cancer or any other complications.
A study published in the journal Sciencefeatures the external development of a mouse embryo. With the use of embryonic stem cells, developmental biologist Magdalena Zernicka-Goetz and her team at the University of Cambridge were able to replicate a living mouse embryo.
By combining genetically modified mouse embryonic stem cells (ESCs) and extra-embryonic trophoblast stem cells (TSCs) in a 3D gel scaffold, Zernicka-Goetz’s team was able to drive the development of a synthetic embryo very similar to that of natural embryos. The synthetic embryo mirrored a natural embryo – not only did it form anatomically correct regions, but it also formed them at the right time. This means that the stem cells utilized are able to “talk” to one another to guide the specific steps of development.
The synthetic embryo cannot develop into a healthy fetus—largely due to the fact that a third stem cell would be required to develop a yolk sac, the part of the embryo that provides nourishment. The current conditions that allow the synthetic embryo to develop are not optimal for placenta development either, closing the door entirely on a synthetic fetus. The rest of methods can be duplicated for others to emulate, however.
Many research teams in the past have tried to develop the embryo in synthetic form with limited success. Zernicka-Goetz’s team introduced a 3D extracellular matrix into the equation, which made it possible for the stem cells to operate and form the synthetic embryo. The team’s discovery is a promising sign for the future of embryo research.
The Science of Tomorrow
Development in the early stages of the embryo is important to pregnancies, with more than two-thirds of miscarriages, linked to genetic glitches during fertilization. With the advent of the synthetic embryo, Zernicka-Goetz noted to The Guardian that researchers can conduct studies “on key stages of the human development without actually having to work on embryos.”
Currently, researchers are shackled by a shortage of human embryos to study, as scientists depend on donated eggs from IVF clinics. Embryonic stem cells, on the other hand, are in limitless supply and avoid the ethical dilemma posed by donated or discarded embryos.
The team’s next step is to successfully synthesize a human embryo analog – they are convinced that its inception will push us forward in studying our earliest stages of development.
One of the most common causes of hearing loss is damage to the thousands of hair cells found within the inner ear. These hair cells detect and translate sound waves into nerve signals, enabling us to hear sound. As crucial as these hair cells are to hearing, these are susceptible to damage caused by excessive noise, old age, or certain medications. Once these hair cells are destroyed in a human ear, they don’t regenerate.
In 2012, lead scientist Albert Edge discovered stem cells in the ear called Lgr5+ cells. These were also found in the lining of human intestines, where they actively regenerate every eight days. Edge’s team found a way to convince these stem cells to develop into hair cells instead of intestinal cells. The process took a great deal of time, however, and it only yielded 200 hair cells. Now, the team had managed to grow 11,500 hair cells from the Lgr5+ cells in mice, which are among the few mammals whose cells can regenerate when they are newly born.
The researchers achieved this higher yield by adding a new step to their process. After taking the Lgr5+ cells from the mice, they coaxed them to divide within a special growth medium. This increased the number of Lgr5+ cells two-thousandfold. The stem cells were then moved to a different kind of growth culture, at which point certain chemicals were added that turned the Lgr5+ cells into hair cells.
“A Big Advance”
Each human ear has about 16,000 hair cells in its cochlea, the actual hearing organ found deep in the ear canal. These hair cells are divided into outer hair cells and inner hair cells, each with a specialized role in handling sound.
While these lab-grown hair cells seem to have many characteristics similar to these outer and inner hair cells, Edge admits that they may not yet be fully functional. His team tested their technique on a sample of healthy ear tissue taken from a 40-year-old brain tumor patient that underwent a labyrinthectomy. The isolated adult human stem cells did differentiate into hair cells, but not as robustly as the mouse cells had.
Still, neuroscience professor and hair-cell regeneration expert Jeff Corwin from the University of Virginia School of Medicine told Live Science he found the research to be “a very impressive study…by a dream team of scientists.” Corwin, who wasn’t involved in the study, called it “a big advance” in sensory hearing cell regeneration. “You can see in their paper that they are perfecting their technique as they go along,” he added.
While the team works to continue improving their methods, Edge said that their lab-grown hair cells may have one immediate application — large sets of the cells can be made and used to test drugs and identify which compounds can heal damaged hair cells or induce regeneration.
Gene therapy has been available for quite some time now. Advances in modern medical science, particularly in stem cell research, have made it possible to use DNA to compensate for malfunctioning genes in humans. The therapies have even proven effective for treating rare forms of diseases. Now, a research team in France has shown that gene therapy may be used to cure one of the most common genetic diseases in the world.
The team, led by Marina Cavazzana at the Necker Children’s Hospital in Paris, conducted stem cell treatment on a teenage boy with sickle cell disease. The disease alters the blood through beta-globin mutations, which cause abnormalities in the blood protein hemoglobin. These abnormalities cause the blood cells (which have an irregular shape, like a sickle, hence their name) to clump together. Patients with sickle cell disease usually need transfusions to clear the blockages their cells cause, and some are able to have bone marrow transplants. About 5 percent of the global population has sickle cell disease, according to the WHO. In the United States alone, the CDC reports that approximately 100,000 people have sickle cell disease.
“The patient is now 15 years old and free of all previous medication,” Cavazzana said when discussing the outcome of their study. “He has been free of pain from blood vessel blockages, and has given up taking opioid painkillers.” Their research is published in the the New England Journal of Medicine.
The Wonders of Gene Therapy
The particular treatment given to the teenage boy at Necker Children’s Hospital began when he was 13 years old. The team took bone marrow stem cells from the boy and added mutated versions of the gene that codes for beta-globin before putting these stem cells back into the boy’s body. The mutated genes were designed to stop hemoglobin from clumping together and blocking blood vessels — the hallmark of sickle cell disease.
Two years later, the boy’s outcome looks promising. “All the tests we performed on his blood show that he’s been cured, but more certainty can only come from long-term follow-up,” Cavazzan said. Her team also treated seven other patients who also showed “promising” progress.
If the method shows success in larger scale clinical trials, “it could be a game changer,” said Deborah Gill at the University of Oxford, “The fact the team has a patient with real clinical benefit, and biological markers to prove it, is a very big deal.”
Our blood changes as we age due to epigenetics, a process by which our gene expression is silenced or activated over time, without modification of the genetic code itself. With this in mind, the team of researchers at the University of Lunds took a look at the hematopoietic stem cells (HSC) of aged mice to see if they could unlock the mysteries of how our cells age.
HSC cells are progenitors to all other blood cells. As we age, scientists believe that our cells age, too. Aging blood cells mean we’re more vulnerable to diseases like leukemia, which target those cells specifically. Likewise, the researchers at the University of Lunds observed reduced functionality of the blood of their aging mice. But when the old mice were provided with induced pluripotent stem (iPS) cells — essentially a batch of fresh stem cells — something quite fascinating happened. The iPS cells served as a “reset button”, reprogramming the blood stem cells and sparking a rejuvenation of sorts. Researchers observed that the progenitor HSC cells in the old mice began to produce blood cells functionally similar to those seen in younger mice.
The group’s data suggests that HSC aging can be reversed by the introduction of iPS cells. It’s important to note, however, that these changes in blood cell production do not primarily occur due to mutations — but because of epigenetic changes in gene expression over time. With their encouraging results, the research team is hopeful they may be closer to developing therapies that could reduce the incidence of blood disorders, including the three main types of blood cancers and over 100 blood-related diseases.
Our knowledge of and ability to use stem cell technology has been growing in recent years, and now, a proof of principle study has shown that it is possible to grow and then successfully transplant organs of one species in the body of another — a stem cell chimera, so to speak. The study, published online in the journalNature, sets up the possibility of growing transplantable human tissue using another species as the host.
Researchers Hiromitsu Nakauchi and colleagues were able to demonstrate that mouse pancreatic islets grown inside rats and then transplanted into diabetic mice could survive and function normally for prolonged periods of time. The team injected mouse pluripotent stem cells into embryonic rats that were bred to be incapable of growing their own pancreases. Once the rats were adults, their pancreases, which were comprised mostly of mouse cells, were transplanted into diabetic mice. The transplanted organs, with immunosuppression applied only in the first five days after the transplant, were able to sustain blood glucose levels in the diabetic mice for over a year.
“Pancreatic islet transplantation for severe diabetes provides a clinically relevant model to address this question,” the study notes, the question in reference being stem cell transplant survivability. “We therefore sought to determine whether mouse pancreatic islets isolated from pancreata derived in rats through interspecies blastocyst complementation (denoted as mouseR) could induce long-term glycaemic control in mice with streptozotocin (STZ)-induced diabetes.”
Solving Donor Deficiency Issues
The study comes as a viable solution to the problem of organ donor deficiency. This is especially relevant since organ transplantation “remains the only cure for a growing number of patients suffering from a broad range of debilitating and fatal diseases,” the researchers write. “An increasing clinical burden with continued donor deficiency means that, for example, over 76,000 patients in the U.S. are currently waiting for a transplant operation.”
Of course, applying the study to human situations still remains a distant possibility. For one, there are technical challenges that need to be overcome — after all, the study is still in its proof-of-concept phase. Organs for human transplant need to be generated in animals that closely resemble humans in both size and evolutionary distance, such as sheep, pig, or non-human primates, the researchers noted. While researchers have previously grown human body parts using other species as the host (such as the well-known human ear on the back of a rat), we have yet to transplant any to human patients.
That brings up the ethical and legal questions that need to be addressed for any stem cell-related applications, including the debate over which kinds of stem cells could and should be approved for human applications. Setting these issues aside for now, Nakauchi and his team were able to confirm that pluripotent stem cells have the potential to produce replacement cells and tissues of an unlimited quantity. More over, they managed to prove that these can survive, normalize, and function long after transplant. With continuous study and research, it remains only a matter of time before the method could be adapted for human application.
The potential of stem cells for various treatments keeps scientists, like a team at the Salk Institute, to continually develop ways to produce human/animal (chimera) stem cells. Now, the chimera that these researchers are developing is not the multi-headed, fire-breathing monster of Greek mythology, but rather a genetic chimera. A genetic chimera is simply a singular organism made up of cells coming from different zygotes.
This team of Salk Institute researchers, led by Juan Carlos Izpisua Belmonte, are aiming to develop a chimera made of both human and pig stem cells. “The ultimate goal is to grow functional and transplantable tissue or organs, but we are far away from that,” said Izpisua Belmonte, researcher and author of the study published in the journal Cell. “This is an important first step.”
As expected, developing fully grown three-dimensional tissues and organs from stem cells in a petri dish wasn’t easy. “It’s like when you try to duplicate a key. The duplicate looks almost identical, but when you get home, it doesn’t open the door. There is something we are not doing right,” Izpisua Belmonte said. “We thought growing human cells in an animal would be much more fruitful. We still have many things to learn about the early development of cells.”
Izpisua Belmonte and Salk scientist Jun Wu’s experiment began with the production of a rat/mouse chimera, something that’s already been done by other scientists in 2010. They introduced rat cells into mouse embryos and allowed these to mature. They then proceeded to introduce human cells into an organism, opting for cows and pigs because their organs more closely resemble human organs in terms of size. They experimented with about 1,500 pig embryos over a four-year period.
Several different forms of human stem cells were injected into pig embryos to determine which could best survive. Of these, those that showed a high survival rate and the most potential to continually develop were “intermediate” pluripotent stem cells. “Intermediate cells are somewhere in between” the two cell types, “naive” cells and “primed” cells, Wu explained. The former have unrestricted development and resemble cells in an earlier developmental origin. The later have already developed further but remain pluripotent.
The human cells that survived formed a human/pig chimera embryo. These were implanted into sows and were allowed to develop for three to four weeks. “This is long enough for us to try to understand how the human and pig cells mix together early on without raising ethical concerns about mature chimeric animals,” Izpisua Belmonte said.
However, even with the best-performing human stem cells, Wu stated that the level of contribution to the chimeric embryo was low. But this isn’t necessarily a bad thing. One concern about human/animal chimera embryos is that they would develop to be too human. “At this point, we wanted to know whether human cells can contribute at all to address the ‘yes or no’ question,” said Izpisua Belmonte. “Now that we know the answer is yes, our next challenge is to improve efficiency and guide the human cells into forming a particular organ in pigs.” The researchers are now relying on CRISPR to do this, editing pig genomes to open gaps that the human cells can fill in.
The goal of growing fully functional and transplantable tissue or organs is still far away. Thankfully, this team is not intending to create fully grown chimera organisms (the ethical issues of this “mad science” would be too difficult). For now, the researchers are happy that this study can help scientists understand how human stem cells grow and specialize. The human/pig chimera embryos could also give insights into early human development and disease onset.
The technology behind lab-cultured meat products is rapidly advancing. It’s possible that we will start seeing these kinds of products being sold right alongside their traditionally farmed cousins. The advent of a more sustainable means of keeping meat on tables has shed new light on the contentious topic of the impact livestock farming has on the environment.
According to the Food and Agriculture Organization of the United Nations (FAO), twenty-six percent of the ice-free land on Earth is used for livestock feed production. Further, “[e]ach year 13 billion hectares (32.1 billion acres) of forest area are lost due to land conversion for agricultural uses as pastures or cropland, for both food and livestock feed crop production.” Livestock farming contributes to 14.5 percent of all anthropogenic (human caused) greenhouse gas emissions, meaning 7.1 gigatonnes of carbon dioxide are released from the practice. The National Institute of Environmental Health Science estimates that by 2050 livestock populations are expected to double.
The environmental impact of traditional meat production is not the only downside of the practice. There are also very serious health concerns involved for both animals and humans. Animals on factory farms are often confined in poor, overcrowded, conditions and are unable to engage in natural behavior. This can lead to illness, physical alterations, or even death.
Further, in order to make our meat cheaper by fighting disease and making the animals grow faster, they will be given antibiotic growth promoters. This wanton distribution of powerful antibiotics is one of the leading causes of the rapid spread of drug-resistant bacteria, also known as superbugs. Recently, a superbug claimed its first victim in the U.S. This is an ongoing problem only set to get worse without significant changes.
Lab-grown meat products could very well be a major part of that change. The cost of cultivating meat in a lab has dramatically decreased in the last few years. A team of Dutch scientists were able to grow a burger for a total cost of $330,000, and just a few months ago, a company out of the United States called Memphis Meats was able to serve up the world’s first lab-grown meatball for the cost of $18,000 per pound. This is of course nowhere near affordable for mass consumption. Both teams believe that the technology will continue to advance rapidly, allowing for products to show up in grocery stores and restaurants within a few years.
Instead of cultivating entire animals to harvest their meat, companies are able to simply take self-renewing stem cells from animals and cultivate those in a brewery-like atmosphere. Memphis Meats even states that their facilities will be open to the public much like a beer brewery.
Better Between the Buns
The conditions of the labs are also an important factor to show the greater benefits of lab-grown meats over conventional animal proteins. The meats are grown in a sterile environment, thus eliminating the need for antibiotics. Also, the conditions do not allow for the growth of dangerous bacteria such as salmonella or e.coli, making the product even safer.
Another aspect of human health that can come from cultured meat is the removal or reduction of saturated fats. Professor Mark Post from Maastricht University was involved in the cultivation of that very first lab-grown burger. He stated, “Stem cells are, in principle, capable of making omega-3 fatty acids. If we can tap into that machinery of the cell, then we could make healthier hamburgers.” Since fats are a critical component contributing to meat flavor, texture, and other desirable characteristics such as juiciness, it is important that cultivated meats retain fat content. However, omega-3 fatty acids are much healthier than saturated fats. Still, a balance must be struck as too much omega-3 can cause the meat to have a fishy taste.
According to Memphis Meats CEO and co-founder, Uma Valeit, the process by which the company creates its product is responsible for 90 percent fewer emissions. Since growing cells doesn’t require acres upon acres of land, the land used to shelter and graze livestock can be reclaimed by nature, at least ideally.
As far-fetched as this idea seems, it’s a possibility that scientists are now exploring after they successfully produced healthy mice using a process called in vitro gametogenesis (IVG). This is a revolutionary method involving embryonic stem cells that are reprogramed to become viable sex cells.
In the mice experiment, scientists made early stage mouse eggs from stem cells and grew them in the lab. Once the eggs matured, they fertilized them with mouse sperm and demonstrated that they could also be successfully implanted into a surrogate female mouse.
It’s important to note that the technology is still in its infancy. Creating eggs from skin cells is a possibility, but at this point, there is still some work to be done before it is truly viable in humans. The success of the mouse model, however, illustrates the opportunities that this technique could offer.
Obviously, IVG is revolutionary for the field of fertility medicine. It gives infertile people hope, especially those who are unable to have children because of cancer treatment. For example, collecting skin cells from patients undergoing chemotherapy means scientists can turn them into healthy eggs or sperm in case they become infertile as a result of treatment.
In short, the technique could render egg donors obsolete. For couples undergoing fertility treatments, they no longer have to choose from just a handful of viable embryos, they could potentially select from a bigger pool. It also makes the biological process of conceiving more democratic. Theoretically, the method can be used to produce egg cells from male skin cells, making it possible for a baby to be created from same-sex couples.
Perhaps as a testament to the promise of this technique, experts are already looking into IVG’s possible consequences this early into the study.
For instance, should the procedure eventually become accessible and inexpensive, we could face the possibility of ‘embryo farming,’ which for some, puts a focus on how this method can devalue human life. Perceived advantages, like making it possible for parents to select from a bigger pool of embryos, also has obvious downsides—like high-tech enabled eugenics.
Combined with advances in gene editing technology, it raises ethical concerns regarding human enhancement and designer babies. And with IVG theoretically making it possible for a baby to have three or more genetic parents, it raises questions regarding the legal rights and responsibilities of each parent.
It’s difficult to predict when technology like this will be ready for use in humans. Right now, any efforts to replicate the same results in primates or humans has proved unsuccessful. But the study is steadily moving forward, and as the authors pointed out:
[…] With science and medicine hurtling forward at breakneck speed, the rapid transformation of reproductive and regenerative medicine may surprise us. Before the inevitable, society will be well advised to strike and maintain a vigorous public conversation on the ethical challenges of IVG.
Nobody likes a toothache. At the slightest sign of a damaged tooth, many of us run to our dentists so they can fill the cavities caused by trauma or infection — or perhaps just a persistent sweet tooth. Researchers from King’s College London may have found a better way to deal with damaged teeth, one that doesn’t involve just plugging the holes. Instead, their method stimulates the renewal of living stem cells within the teeth.
Usually, dental fillings — those man-made tooth cements — are composed of calcium or some silicon-based product. While they do cover the soft pulp within a tooth that gets exposed in cases of damage (thus causing us pain), the fillings remain in the teeth indefinitely. Because they never degrade, the fillings prevent the normal mineral level of the tooth from being completely restored, according to the study, which is published in the journal Scientific Reports.
When our teeth sustain minor damage, the body naturally produces dentine, a thin band of protective coating that seals the tooth pulp, keeping it from prolonged exposure that may cause infection. However, it is not enough to effectively fix larger cavities, which is why a trip to the dentist is in order. The King’s College researchers developed a method that would stimulate the stem cells contained in tooth pulp to produce new dentine. Their method allows teeth to use their natural, biological ability to repair larger cavities, thus reducing the need for fillings or cement.
The treatment was delivered by applying biodegradable collagen sponges that contained low doses of small molecule glycogen synthase kinase (GSK-3) to the damaged tooth. The sponge would degrade over time, unlike dental fillings, and would be replaced by new dentine. “The simplicity of our approach makes it ideal as a clinical dental product for the natural treatment of large cavities, by providing both pulp protection and restoring dentine,” explained lead author Paul Sharpe in a press release.
A Natural Repair System
One of the small molecules the researchers used to stimulate the stem cell renewal included Tideglusib. This GSK-3 inhibitor has already been through clinical trials and used to treat neurological disorders, such as Alzheimer’s disease. Furthermore, the collagen sponges used within the treatment are already commercially available and clinically approved. This means that this natural dentine-inducing tooth repair method could easily be fast-tracked into actual dental treatment use within clinics.
This is a truly natural alternative to cement fillings, which can deteriorate and need replaced over time, and through scientific advances like this one, we are finding more and more ways to improve upon the body’s natural defenses, which are often the best at combating damage and disease. Just think — if this method is approved, you may have already had your last man-made dental filling.
Researchers from the Heart Research Institute (HRI) have developed a 3D bioprinter, the first of its kind in Australia, that could replace a patient’s damaged cells after a heart attack.
“When patients come into the clinic, they would provide us with their cells from their skin,” HRI scientist Dr Carmine Gentile explained. “Those cells can generate stem cells and then heart cells.” The resulting patch of beating cardiac cells can be stuck directly to a damaged organ following an attack. In order to be sure the patch is the right size and shape, each patient’s heart is first scanned to map the damage.
According to Gentile, “the cells behave[d] like a real heart. This is a striking finding that we have been able to identify in our lab.”
Initially a method used to produce various tools and equipment, 3D printing has been quickly adapted to medicine. All bioprinters are still experimental, however, since their output has not yet been rigorously tested by medical experts.
Bioprinting is no doubt more effective than current methods of coping with heart attacks, which force the heart vessels open to facilitate increased blood flow. Theoretically, this print-and-patch method should work for all patients without fear of rejection.
“We haven’t succeeded in finding a solution in replacing the scar muscle or to regenerate hearts. That’s one of the holy grails of cardiovascular research at the moment and this is just one potential exciting solution,” said Kolling Institute’s Gemma Figree, a cardiologist.
This is especially relevant since, according to The Heart Foundation, someone in the US suffers a heart attack every 34 seconds, while someone dies from a heart-related disease every 60 seconds. The costs of heart disease pile up to a hefty $320.1 billion, which also accounts for foregone productivity and healthcare expenditures.
Experts from the HRI believe that the synthetic heart cells could even be used for testing drugs, particularly the side effects that might affect the patient. According to the researchers, these bioprinting methods could be available in about five years. The process will be costly however, as it is expensive to collect biological material to 3D bio-print a patch.