Stem Cell Roundup: Backup cells to repair damaged lungs; your unique bowels; and California Cures, 71 ways CIRM is changing the face of medicine

It’s good to have a backup plan

3D illustration of Lungs, medical concept.

Our lungs are amazing things. They take in the air we breathe and move it into our blood so that oxygen can be carried to every part of our body. They’re also surprisingly large. If you were to spread out a lung – and I have no idea why you would want to do that – it would be almost as large as a tennis court.

But lungs are also quite vulnerable organs, relying on a thin layer of epithelial cells to protect them from harmful materials in the air. If those materials damage the lungs our body calls in local stem cells to repair the injury.

Now researchers at the University of Iowa have identified a new group of stem cells, called glandular myoepithelial cells (MECs), that also appear to play an important role in repairing injuries in the lungs.

These MECs seem to be a kind of “reserve” stem cell, waiting around until they are needed and then able to spring into action and develop into new replacement cells in the lungs.

In a news release study author Preston Anderson, said these cells could help develop new approaches to lung regeneration:

“We demonstrated that MECs can self-renew and differentiate into seven distinct cell types in the airway. No other cell type in the lung has been identified with this much stem cell plasticity.”

The study is published in Cell Stem Cell.

Your bowels are unique

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Not to worry, that’s a plastic model of  a bowel

If you are eating as you read this, you should either put your food down or skip this item for now. A new study on bowel cancer says that every tumor is unique and every cell within that tumor is also genetically unique.

Researchers in the UK and Netherlands took samples of normal bowel tissue and cancerous bowel tissue from three people with colorectal cancer. They then grew these in the labs and turned them into mini 3D organoids, so they could study them in greater detail.

In the study, published in the journal Nature, the researchers say they found that tumor cells, not surprisingly, had many more mutations than normal cells, and that not only was each bowel cancer genetically different from each other, but that each cell they studied within that cancer was also different.

In a news release, Prof Sir Mike Stratton, joint corresponding author on the paper from the Wellcome Sanger Institute, said:

“This study gives us fundamental knowledge on the way cancers arise. By studying the patterns of mutations from individual healthy and tumour cells, we can learn what mutational processes have occurred, and then look to see what has caused them. Extending our knowledge on the origin of these processes could help us discover new risk factors to reduce the incidence of cancer and could also put us in a better position to create drugs to target cancer-specific mutational processes directly.”

California Cures: a great title for a great book about CIRM

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CIRM Board Chair Jonathan Thomas (L) and Don Reed

One of the first people I met when I started working at CIRM was Don Reed. He impressed me then with his indefatigable enthusiasm, energy and positive outlook on life. Six years later he is still impressing me.

Don has just completed his second book on stem cell research charting the work of CIRM. It’s called “California Cures: How the California Stem Cell Research Program is Fighting Your Incurable Disease”. It’s a terrific read combining stories about stem cell research with true tales about Al Jolson, Enrico Caruso and how a dolphin named Ernestine burst Don’s ear drum.

On his website, Stem Cell Battles, Don describes CIRM as a “scrappy little stage agency” – I love that – and says:

“No one can predict the pace of science, nor say when cures will come; but California is bringing the fight. Above all, “California Cures” is a call for action. Washington may argue about the expense of health care (and who will get it), but California works to bring down the mountain of medical debt: stem cell therapies to ease suffering and save lives. We have the momentum. We dare not stop short. Chronic disease threatens everyone — we are fighting for your family, and mine!”

 

Stem cell study holds out promise for kidney disease

Kidney failure

Image via youtube.com

Kidney failure is the Rodney Dangerfield of diseases, it really doesn’t get the respect it deserves. An estimated 660,000 Americans suffer from kidney failure and around 47,000 people die from it every year. That’s more than die from breast or prostate cancer. But now a new study has identified a promising stem cell candidate that could help in finding a way to help repair damaged kidneys.

Kidneys are the body’s waste disposal system, filtering our blood and cleaning out all the waste products. Our kidneys have a limited ability to help repair themselves but if someone suffers from chronic kidney disease then their kidneys are slowly overwhelmed and that leads to end stage renal disease. At that point the patient’s options are limited to dialysis or an organ transplant.

Survivors hold out hope

Italian researchers had identified some cells in the kidneys that showed a regenerative ability. These cells, which were characterized by the expression of a molecule called CD133, were able to survive injury and create different types of kidney cells.

Researchers at the University of Torino in Italy decided to take these findings further and explore precisely how CD133 worked and if they could take advantage of that and use it to help repair damaged kidneys.

In their findings, published in the journal Stem Cells Translational Medicine, the researchers began by working with a chemotherapy drug called cisplatin, which is used against a broad range of cancers but is also known to cause damage to kidneys in around one third of all patients. The team found that CD133 was an important factor in helping those damaged kidneys recover. They also found that CD133 prevents aging of kidney progenitor cells, the kind of cell needed to help create new cells to repair the kidneys in future.

Hope for further research

The finding opens up a number of possible lines of research, including exploring whether infusions of CD133 could help patients whose kidneys are no longer able to produce enough of the molecule to help repair damage.

In an interview in DD News, Dr. Anthony Atala, Director of the Wake Forest Institute for Regenerative Medicine – praised the research:

“This is an interesting and novel finding. Because the work identifies mechanisms potentially involved in the repair of tissue after injury, it suggests the possibility of new therapies for tissue repair and regeneration.”

CIRM is funding several projects targeting kidney disease including four clinical trials for kidney failure. These are all late-stage kidney failure problems so if the CD133 research lives up to its promise it might be able to help people at an earlier stage of disease.

Cold temps nudge stem cells to boost “good” fat, may point to obesity remedies

Newborn babies may not be able to walk or talk but they can do something that makes adults very jealous: burn extra calories without exercising. This feat is accomplished with the help of brown fat which is abundant in infants (and hibernating animals) but barely detectable in adults. However, a new study in Scientific Reports shows that cold temperatures can nudge mesenchymal stem cells – found in the bone marrow – toward a brown fat cell fate, a finding that may uncover new strategies for combating obesity and other metabolic diseases.

Brown-and-White-adipose-tissue

Side by side comparision of brown fat, or adipose, cells and white fat cells.
Image: AHAJournals.org

So, what’s so magical about cells that carry brown fat, the so-called “good” fat? Like the more common “bad’ white fat cells, brown fat cells store energy in the form of fat droplets and can burn that energy to meet the demands of the body’s functions like pumping the heart and moving the limbs. But brown fat can also burn calories independent of the body’s energy needs. It’s like stepping on a car’s clutch and gas pedal at the same time: the body burns the fuel but doesn’t do any usable work, so those calories just dissipate as heat. This source of heat is critical for babies because they are not yet able to regulate their own body temperature and lose heat rapidly.

Scientists have known for quite some time that cold temperatures stimulate the production of brown fat but didn’t know exactly why (a CIRM-funded study we blogged about last week identified a protein that also boosts brown fat production). In the current study, a team at the University of Nottingham in the U.K., examined the effect of cold temperature on the fate of bone marrow-derived mesenchymal stem cells which give rise to both white and brown fat tissue as well as bone, cartilage and muscle. Petri dishes containing the cells were placed in incubators at 89°F (32°C) and stimulated to become fat cells. That may not seem cold, but if your core body temperature went that low (instead of the normal 98.6F) you would be beyond shivering, close to collapsing and in need of an emergency room.

With that temperature drop, the researcher observed a “browning” of the stem cells towards a brown fat cell fate. The brown color, in case you’re interested, is cause by the increased number of mitochondria within the cells. These “power factories” of the cell are the source of the heat generation. This result has promising implications for adults struggling with their body weight.

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Virginie Sottile

“The good news from these results is that our cells are not pre-programmed to form bad fat and our stem cells can respond if we apply the right change in lifestyle,” explained Dr Virginie Sottile, one of the team leaders on the project, in a press release.

 

Ok, I know what you’re thinking: moving to Antarctica to lose weight is not my idea of a doable lifestyle change! That’s a point well taken. But the ultimate goal for the researchers is to use this cell system to more carefully study the cellular events that occur under reduced temperatures. This type of inquiry could help identify drug targets that mimic the effects of colder temperatures:

“The next step in our research is to find the actual switch in the cell that makes it respond to the change of temperature in its environment,” said Dr Sottile. “That way, we may be able to identify drugs or molecules that people could swallow that may artificially activate the same gene and trick the body into producing more of this good fat.”

Stem Cell Round: Improving memory, building up “good” fat, nanomedicine

Stem Cell Photo of the Week

roundup03618In honor of brain awareness week, our featured stem cell photo is of the brain! Scientists at the Massachusetts General Hospital and Harvard Stem Cell Institute identified a genetic switch that could potentially improve memory during aging and symptoms of PTSD. Shown in this picture are dentate gyrus cells (DGC) (green) and CA3 interneurons (red) located in the memory-forming area of the brain known as the hippocampus. By reducing the levels of a protein called abLIM3 in the DGCs of older mice, the researchers were able to boost the connections between DGCs and CA3 cells, which resulted in an improvement in the memories of the mice. The team believes that targeting this protein in aging adults could be a potential strategy for improving memory and treating patients with post-traumatic stress disorder (PTSD). You can read more about this study in The Harvard Gazette.

New target for obesity.
Fat cells typically get a bad rap, but there’s actually a type of fat cell that is considered “healthier” than others. Unlike white fat cells that store calories in the form of energy, brown fat cells are packed with mitochondria that burn energy and produce heat. Babies have brown fat, so they can regulate their body temperature to stay warm. Adults also have some brown fat, but as we get older, our stores are slowly depleted.

In the fight against obesity, scientists are looking for ways to increase the amount of brown fat and decrease the amount of white fat in the body. This week, CIRM-funded researchers from the Salk Institute identified a molecule called ERRg that gives brown fat its ability to burn energy. Their findings, published in Cell Reports, offer a new target for obesity and obesity-related diseases like diabetes and fatty liver disease.

The team discovered that brown fat cells produce the ERRg molecule while white fat cells do not. Additionally, mice that couldn’t make the ERRg weren’t able to regulate their body temperature in cold environments. The team concluded in a news release that ERRg is “involved in protection against the cold and underpins brown fat identity.” In future studies, the researchers plan to activate ERRg in white fat cells to see if this will shift their identity to be more similar to brown fat cells.

brownfat_mice

Mice that lack ERR aren’t able to regulate their body temperature and are much colder (right) than normal mice (left). (Image credit Salk Institute)

Tale of two nanomedicine stories: making gene therapies more efficient with a bit of caution (Todd Dubnicoff).
This week, the worlds of gene therapy, stem cells and nanomedicine converged for not one, but two published reports in the journal American Chemistry Society NANO.

The first paper described the development of so-called nanospears – tiny splinter-like magnetized structures with a diameter 5000 times smaller than a strand of human hair – that could make gene therapy more efficient and less costly. Gene therapy is an exciting treatment strategy because it tackles genetic diseases at their source by repairing or replacing faulty DNA sequences in cells. In fact, several CIRM-funded clinical trials apply this method in stem cells to treat immune disorders, like severe combined immunodeficiency and sickle cell anemia.

This technique requires getting DNA into diseased cells to make the genetic fix. Current methods have low efficiency and can be very damaging to the cells. The UCLA research team behind the study tested the nanospear-delivery of DNA encoding a gene that causes cells to glow green. They showed that 80 percent of treated cells did indeed glow green, a much higher efficiency than standard methods. And probably due to their miniscule size, the nanospears were gentle with 90 percent of the green glowing cells surviving the procedure.

As Steve Jonas, one of the team leads on the project mentions in a press release, this new method could bode well for future recipients of gene therapies:

“The biggest barrier right now to getting either a gene therapy or an immunotherapy to patients is the processing time. New methods to generate these therapies more quickly, effectively and safely are going to accelerate innovation in this research area and bring these therapies to patients sooner, and that’s the goal we all have.”

While the study above describes an innovative nanomedicine technology, the next paper inserts a note of caution about how experiments in this field should be set up and analyzed. A collaborative team from Brigham and Women’s Hospital, Stanford University, UC Berkeley and McGill University wanted to get to the bottom of why the many advances in nanomedicine had not ultimately led to many new clinical trials. They set out looking for elements within experiments that could affect the uptake of nanoparticles into cells, something that would muck up the interpretation of results.

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imaging of female human amniotic stem cells incubated with nanoparticles demonstrated a significant increase in uptake compared to male cells. (Green dots: nanoparticles; red: cell staining; blue: nuclei) Credit: Morteza Mahmoudi, Brigham and Women’s Hospital.

In this study, they report that the sex of cells has a surprising, noticeable impact on nanoparticle uptake. Nanoparticles were incubated with human amniotic stem cells derived from either males or females. The team showed that the female cells took up the nanoparticles much more readily than the male cells.  Morteza Mahmoudi, PhD, one of the authors on the paper, explained the implications of these results in a press release:

“These differences could have a critical impact on the administration of nanoparticles. If nanoparticles are carrying a drug to deliver [including gene therapies], different uptake could mean different therapeutic efficacy and other important differences, such as safety, in clinical data.”

 

It’s World Kidney Day: Highlighting CIRM’s Investments in Treating Kidney Failure

WKD-Logo-HiToday is World Kidney Day. Hundreds of events across the globe are taking place “to raise awareness of the importance of our kidneys to our overall health and to reduce the frequency and impact of kidney disease and its associated health problems worldwide.” (Side note: in recognition that today is also International Women’s Day, World Kidney Day’s theme this year is “Kidney’s & Women: Include, Value, Empower.)

To honor this day, we’re highlighting how CIRM is playing its part in that mission. The infographic below provides big picture summaries of the four CIRM-funded clinical trials that are currently testing stem cell-based therapies for kidney failure, a condition that affects well over 600,000 Americans.

When a person’s kidneys fail, their body can no longer filter out waste products and extra fluid from the blood which leads to life-threatening complications. About 30% of those affected in the U.S. have organ transplants. Due to the limited availability of donor organs, the other 70% need dialysis, a blood filtration therapy, that requires several trips a week to a special clinic.

Both treatment options have serious limitations. Organ recipients have to take drugs that prevent organ rejections for the rest of their lives. Over time, these drugs are toxic and can increase a patient’s risk of infection, heart disease, cancer and diabetes. In the case of dialysis treatment, the current procedure uses a plastic tube called a shunt to connect to a patient’s vein. These shunts are far from ideal and can lead to infection, blood clots and can be rejected by the patient’s immune system. These complications probably play a role in the average life expectancy of 5-10 years for dialysis patients.

Four CIRM-funded clinical trials aim to circumvent these drawbacks. Humacyte has received over $24 million from the Agency to support two clinical trials that are testing an alternative to the plastic shunt used in dialysis treatment. The company has developed a bioengineered vessel that is implanted in the patient’s arm and over time is populated with the patient’s own stem cells which develop into a natural blood vessel. The trials will determine if the bioengineered vessel is superior to the shunt in remaining open for longer periods of time and with lower incidence of interventions due to blood clots and infections.

The other two CIRM-funded trials, one headed by Stanford University and the other by Medeor Therapeutics, aims to eliminate the need for long-life, anti-rejection medicine after kidney transplant. Both trials use a similar strategy: blood stem cells and immune cells from the organ donor are infused into the patient receiving the organ. If all goes as planned, those donor cells will engraft into and mix with the recipient’s immune system, making organ rejection less likely and ending the need for immune-system suppressing drugs.

For more details visit our Clinical Trial Dashboard.

MonthofCIRM_Kidney3b

Friday Roundup: A better kind of blood stem cell transplant; Encouraging news from spinal cord injury trial; Finding an “elusive” cell that could help diabetics

Cool Instagram image of the week:

Pancreatic Progenitors

Diabetes Research Institute scientists have confirmed that the unique stem cells reside within large ducts of the human pancreas. Two such ducts (green) surrounded by three islets (white) are shown. [Diabetes Research Institute Foundation]

Chemo- and radiation-free blood stem cell transplant showing promise

Bubble baby disease, also known as severe combined immunodeficiency (SCID), is an inherited disorder that leaves newborns without an effective immune system. Currently, the only approved treatment for SCID is a blood stem cell transplant, in which the patient’s defective immune system cells are eliminated by chemotherapy or radiation to clear out space for cells from a healthy, matched donor. Even though the disease can be fatal, physicians loathe to perform a stem cell transplant on bubble baby patients:

Shizuru“Physicians often choose not to give chemotherapy or radiation to young children with SCID because there are lifelong effects: neurological impairment, growth delays, infertility, risk of cancer, etc.,” says Judith Shizuru, MD, PhD, professor of medicine at Stanford University.

To avoid these complications, Dr. Shizuru is currently running a CIRM-funded clinical trial testing a gentler approach to prepare patients for blood stem cell transplants. She presented promising, preliminary results of the trial on Tuesday at the annual meeting of Stanford’s Center for Definitive and Curative Medicine.

Trial participants are receiving a protein antibody called CD117 before their stem cell transplant. Previous studies in animals showed that this antibody binds to the surface of blood stem cells and blocks the action of a factor which is required for stem cell survival. This property of CD117 provides a means to get rid of blood stem cells without radiation or chemotherapy.

Early results in two participants indicate that, 6 and 9 months after receiving the CD117 blood stem cell transplants, the donor cells have successfully established themselves in the patients and begun making immune cells.

Spinal cord injury trial reports more promising results:

AsteriasRegular readers of our blog will already know about our funding for the clinical trial being run by Asterias Biotherapeutics to treat spinal cord injuries. The latest news from the company is very encouraging, in terms of both the safety and effectiveness of the treatment.

Asterias is transplanting stem cells into patients who have suffered recent injuries that have left them paralyzed from the neck down. It’s hoped the treatment will restore connections at the injury site, allowing patients to regain some movement and feeling in their hands and arms.

This week the company announced that of the 25 patients they have treated there have been no serious side effects. In addition:

  • Magnetic Resonance Imaging (MRI) scans show that in more than 90 percent of the patients the cells appear to show signs of engraftment
  • At least 75 percent of those treated have recovered at least one motor level, and almost 20 percent have recovered two levels

In a news release, Michael Mulroy, Asterias’ President and CEO, said:

“The positive safety profile to date, the evidence supporting engraftment of the cells post-implantation, and the improvements we are seeing in upper extremity motor function highlight the promising findings coming from this Phase 1/2a clinical trial, which will guide us as we work to design future studies.”

There you are! Finding the “elusive” human pancreatic progenitor cells – the story behind our cool Instagram image of the week.

Don’t you hate it when you lose something and can’t find it? Well imagine the frustration of scientists who were looking for a group of cells they were sure existed but for decades they couldn’t locate them. Particularly as those cells might help in developing new treatments for diabetes.

Diabetes-Research-Institute_University-of-Miami-Miller-School-of-MedicineWell, rest easy, because scientists at the Diabetes Research Institute at the University of Miami finally found them.

In a study, published in Genetic Engineering and Biotechnology News, the researchers show how they found these progenitor cells in the human pancreas, tucked away in the glands and ducts of the organ.

In type 1 diabetes, the insulin-producing cells in the pancreas are destroyed. Finding these progenitor cells, which have the ability to turn into the kinds of cells that produce insulin, means researchers could develop new ways to regenerate the pancreas’ ability to function normally.

That’s a long way away but this discovery could be an important first step along that path.

Seeing is believing. Proof a CIRM-funded therapy is making a difference

ThelmaScreenShotFB

Thelma, participant in the CAMELLIA clinical trial

You have almost certainly never heard of Thelma, or met her, or know anything about her. She’s a lady living in England who, if it wasn’t for a CIRM-funded therapy, might not be living at all. She’s proof that what we do, is helping people.

Thelma is featured in a video about a treatment for acute myeloid leukemia, one of the most severe forms of blood cancer. Thelma took part in a clinical trial, called CAMELLIA, at Oxford Cancer Centre in Oxford, UK. The clinical trial uses a therapy that blocks a protein called CD47 that is found on the surface of cancer cells, including cancer stem cells which can evade traditional therapies. The video was shot to thank the charity Bloodwise for raising the funds to pay for the trial.

Prof. Paresh Vyas of Oxford University, who was part of the clinical trial team that treated Thelma, says patients with this condition face long odds.

“Patients with acute myeloid leukemia have the most aggressive blood cancer. We really haven’t had good treatments for this condition for the last 40 years.”

While this video was shot in England, featuring English nurses and doctors and patients, the therapy itself was developed here in California, first at Stanford University under the guidance of Irv Weissman and, more recently, at Forty Seven Inc. That company is now about to test their approach in a CIRM-funded clinical trial here in the US.

This is an example of how CIRM doesn’t just fund research, we invest in it. We help support it at every stage, from the earliest research through to clinical trials. Without our early support this work may not have made it this far.

The Forty Seven Inc. therapy uses the patient’s own immune system to help fight back against cancer stem cells. It’s looking very promising. But you don’t have to take our word for it. Take Thelma’s.

Creating a platform to help transplanted stem cells survive after a heart attack

heart

Developing new tools to repair damaged hearts

Repairing, even reversing, the damage caused by a heart attack is the Holy Grail of stem cell researchers. For years the Grail seemed out of reach because the cells that researchers transplanted into heart attack patients didn’t stick around long enough to do much good. Now researchers at Stanford may have found a way around that problem.

In a heart attack, a blockage cuts off the oxygen supply to muscle cells. Like any part of our body starved off oxygen the muscle cells start to die, and as they do the body responds by creating a layer of scars, effectively walling off the dead tissue from the surviving healthy tissue.  But that scar tissue makes it harder for the heart to effectively and efficiently pump blood around the body. That reduced blood flow has a big impact on a person’s ability to return to a normal life.

In the past, efforts to transplant stem cells into the heart had limited success. Researchers tried pairing the cells with factors called peptides to help boost their odds of surviving. That worked a little better but most of the peptides were also short-lived and weren’t able to make a big difference in the ability of transplanted cells to stick around long enough to help the heart heal.

Slow and steady approach

Now, in a CIRM-funded study published in the journal Nature Biomedical Engineering, a team at Stanford – led by Dr. Joseph Wu – believe they have managed to create a new way of delivering these cells, one that combines them with a slow-release delivery mechanism to increase their chances of success.

The team began by working with a subset of bone marrow cells that had been shown in previous studies to have what are called “pro-survival factors.” Then, working in mice, they identified three peptides that lived longer than other peptides. That was step one.

Step two involved creating a matrix, a kind of supporting scaffold, that would enable the researchers to link the three peptides and combine them with a delivery system they hoped would produce a slow release of pro-survival factors.

Step three was seeing if it worked. Using fluorescent markers, they were able to show, in laboratory tests, that unlinked peptides were rapidly released over two or three days. However, the linked peptides had a much slower release, lasting more than 15 days.

Out of the lab and into animals

While these petri dish experiments looked promising the big question was could this approach work in an animal model and, ultimately, in people. So, the team focused on cardiac progenitor cells (CPCs) which have shown potential to help repair damaged hearts, but which also have a low survival rate when transplanted into hearts that have experienced a heart attack.

The team delivered CPCs to the hearts of mice and found the cells without the pro-survival matrix didn’t last long – 80 percent of the cells were gone four days after they were injected, 90 percent were gone by day ten. In contrast the cells on the peptide-infused matrix were found in large numbers up to eight weeks after injection. And the cells didn’t just survive, they also engrafted and activated the heart’s own survival pathways.

Impact on heart

The team then tested to see if the treatment was helping improve heart function. They did echocardiograms and magnetic resonance imaging up to 8 weeks after the transplant surgery and found that the mice treated with the matrix combination had a statistically improved left ventricular function compared to the other mice.

Jayakumar Rajadas, one of the authors on the paper told CIRM that, because the matrix was partly made out of collagen, a substance the FDA has already approved for use in people, this could help in applying for approval to test it in people in the future:

“This paper is the first comprehensive report to demonstrate an FDA-compliant biomaterial to improve stem cell engraftment in the ischemic heart. Importantly, the biomaterial is collagen-based and can be readily tested in humans once regulatory approval is obtained.”

 

Stem Cell Roundup: New understanding of Huntington’s; how stem cells can double your DNA; and using “the Gary Oldman of cell types” to reverse aging

This week’s roundup highlights how we are constantly finding out new and exciting ways that stem cells could help change the way we treat disease.

Our Cool Stem Cell Image of the Week comes from our first story, about unlocking some of the secrets of Huntington’s disease. It comes from the Laboratory of Stem Cell Biology and Molecular Embryology at The Rockefeller University

Huntington's neurons

A new approach to studying and developing therapies for Huntington’s disease

Researchers at Rockefeller University report new findings that may upend the way scientists study and ultimately develop therapies for Huntington’s disease, a devastating, inherited neurodegenerative disorder that has no cure. Though mouse models of the disease are well-established, the team wanted to focus on human biology since our brains are more complex than those of mice. So, they used CRISPR gene editing technology in human embryonic stem cells to introduce the genetic mutations that cause HD.

Though symptoms typically do not appear until adulthood, the researchers were surprised to find that in their human cell-based model of HD, abnormalities in nerve cells occur at the earliest steps in brain development. These results suggest that HD therapies should focus on treatments much earlier in life.

The researchers observed another unexpected twist: cells that lack Huntingtin, the gene responsible for HD, are very similar to cells found in HD. This suggests that too little Huntingtin may be causing the disease. Up until now, the prevailing idea has been that Huntington’s symptoms are caused by the toxicity of too much mutant Huntingtin activity.

We’ll certainly be keeping an eye on how further studies using this new model affect our understanding of and therapy development for HD.

This study was published in Development and was picked by Science Daily.

How you can double your DNA

dna

As you can imagine we get lots of questions about stem cell research here at CIRM. Last week we got an email asking if a stem cell transplant could alter your DNA? The answer is, under certain circumstances, yes it could.

A fascinating article in the Herald Review explains how this can happen. In a bone marrow transplant bad blood stem cells are killed and replaced with healthy ones from a donor. As those cells multiply, creating a new blood supply, they also carry the DNA for the donor.

But that’s not the only way that people may end up with dual DNA. And the really fascinating part of the article is how this can cause all sorts of legal and criminal problems.

One researcher’s efforts to reverse aging

gary-oldman

Gary Oldman: Photo courtesy Variety

“Stem cells are the Gary Oldman of cell types.” As a fan of Gary Oldman (terrific as Winston Churchill in the movie “Darkest Hour”) that one line made me want to read on in a profile of Stanford University researcher Vittorio Sebastiano.

Sebastiano’s goal is, to say the least, rather ambitious. He wants to reverse aging in people. He believes that if you can induce a person’s stem cells to revert to a younger state, without changing their function, you can effectively turn back the clock.

Sebastiano says if you want to achieve big things you have to think big:

“Yes, the ambition is huge, the potential applications could be dramatic, but that doesn’t mean that we are going to become immortal in some problematic way. After all, one way or the other, we have to die. We will just understand aging in a better way, and develop better drugs, and keep people happier and healthier for a few more years.”

The profile is in the journal Nautilus.

Listen up! Stem cell scientists craft new ears using children’s own cells

Imagine growing up without an ear, or with one that was stunted and deformed. It would likely have an impact on almost every part of your life, not just your hearing. But now scientists in China say they have found a way to help give children born with this condition a new ear, one that is grown using their own cells.

Microtia is a rare condition where children are born with a deformed or underdeveloped outer ear. This is what it can look like.

Microtia ear

In an interview in New Scientist, Dr. Tessa Hadlock, at Massachusetts Eye and Ear Infirmary in Boston, said:

“Children with the condition often feel self-conscious and are picked on, and are unable to wear glasses.”

In the past repairing it required several cosmetic surgeries that had to be repeated as the child grew. But now Chinese scientists say they have helped five children born with microtia grown their own ears.

In the study, published in the journal EBioMedicine, the researchers explained how they used a CT scan of the child’s normal ear to create a 3D mold, using biodegradable material. They took cartilage cells from the child’s ear, grew them in the lab, and then used them to fill in tiny holes in the ear mold. Over the course of 12 weeks the cells continued to multiply and grow and slowly replaced the biodegradable material in the mold.

While the new “ear” was being prepared in the lab, the scientists used a mechanical device to slowly expand the skin on the child’s affected ear. After 12 weeks there was enough expanded skin for the scientists to take the engineered ear, surgically implant it on the child’s head, and cover it with skin.

Over the course of the next two and a half years the engineered ear took on a more and more “natural” appearance. The children did undergo minor surgeries, to remove scar tissue, but other than that the engineered ear shows no signs of complications or of being rejected.

Here is a photo montage showing the pre and post-surgical pictures of a six-year old girl, the first person treated in the study.

Microtia

Other scientists, in the US and UK, are already working on using stem cells taken from the patient’s fat tissue, that are then re-engineered to become ear cells.

Surgeons, like Dr. Hadlock, say this study proves the concept is sound and can make a dramatic difference in the lives of children.

“It’s a very exciting approach. They’ve shown that it is possible to get close to restoring the ear structure.”