Stem cell stories that caught our eye: getting the right cell, an energy booster, history of controversy and a fun video

Here are some stem cell stories that caught our eye this past week. Some are groundbreaking science, others are of personal interest to us, and still others are just fun.

Light used to direct stem cell fate. Stem cells respond to a symphony of cellular signals telling them to remain stem cells or to mature into a specific type of tissue. Much of stem cell biology today has researchers hitting various notes in various rhythms until the score produces a reasonable percentage of the desired tissue.

It’s often a rather discordant process because the cell is not a simple keyboard. A team at the University of California, San Francisco, has used a neat light trick to make the music a little easier to understand. They started with two known facts: that the protein made by the BRN2 gene can drive stem cells to become nerves and that the gene is often turned on in stem cells and they ignore it, choosing to remain stem cells. The UCSF team genetically engineered mouse stem cells so that they could turn on the BRN2 gene with light.

They found that the gene could only drive the production of nerve cells when it was turned on for a relatively long time. They then discovered that the stem cells were responding to another note in the score, a protein that kept the cells in the stem cell state but became depleted after a prolonged period of BRN2 expression.

“There’s lots of promise that we can do these miraculous things like tissue repair or even growing new organs, but in practice, manipulating stem cells has been notoriously noisy, inefficient, and difficult to control,” said Mather Thomson, one of the senior authors on the paper published in Cell Systems and quoted in a university press release widely picked up, including by News Medical. “I think it’s because the cell is not a puppet. It’s an agent that is constantly interpreting information, like a brain. If we want to precisely manipulate cell fate, we have to understand the information-processing mechanisms in the cell that control how it responds to the things we’re trying to do to it.”

Stem cells delivering engines. Jan Nolte, one of our grantees at the University of California, Davis, and editor of the journal Stem Cells, likes to refer to mesenchymal stem cells (MSCs) as little ambulances that rush emergency medical kits to sites of injury. These stem cells that normally hang out in the bone marrow can generate bone, cartilage and blood vessels, but also can deliver a number of chemicals that either tamp down inflammation or summons other repair cells to the scene. The Scientist published a good overview on how MSCs deliver a key repair tool: mitochondria, known as the powerhouse of cells, to cells in need of an energy boost.

Mitochondria are very susceptible to stressors like a heart attack and often are the first parts of a cell to succumb to the stress. While researchers have known for a decade that MSCs can deliver mitochondria to cells, they haven’t known how this happens. They are rapidly gathering that knowledge hoping they to find better ways to harness that particular MSC skill for therapy.

The author walks through a number of discoveries over the past couple years that have begun to paint a picture of this paramedic skill. She also briefly discusses some potential therapies that have been tested in animals.

Embryonic stem cell controversy waning. Pacific Standard, which has become my favorite “thought” magazine even though I have never seen a print copy, published a pretty thorough overview of the early controversy about embryonic stem cells (ESCs) and the many recent scientific advances that may make them unnecessary. The author closes with the fact that for now, advancing those alternatives requires the continued use of ESCs.

Leading with the George W. Bush quote about ESCs being “the leading edge of a series of moral hazards,” he goes on to note that the controversy drove the creation of CIRM and helped Democrats take control of the Senate in 2006. But the bulk of the piece focuses on the alternatives starting with the Nobel Prize-winning discovery of reprogramed adult cells called induced pluripotent stem cells that mimic ESCs. It also covers most recent advances in converting one type of adult cell directly into another type of tissue.

The author closes with a caveat on the ongoing importance of ESCs, at least for now.

“The controversy isn’t over quite yet though—while the newer techniques are immediately useful in research, they have yet to yield any therapies. And because embryonic stem cells are useful for studying how different types of cells develop naturally in the body, they still play an important role in ongoing biomedical research.”

However, he does suggest that eventually, technology will end this controversy.

NOVA video on imagingNOVA video on the brain. Alright, this video only tangentially relates to stem cells and only mentions them toward the end. But it does get at one of the pressing problems in advancing our field: actually seeing what stem cells do at the cell-to-cell and molecular level.

If you are even a casual fan of science, how can you not like a video that starts out with two young scientists using phrases like, “crazy idea,” “wild dream” and “told we’re wasting our time.” It even goes on to talk about “your brain on diapers.” It’s got to be worth the five and a half minutes on the NOVA PBS web site.

It let’s two MIT researchers narrate their effort to image the tiniest of cellular interactions in the brain. Since they found limitations in every existing attempt to see smaller detail, they decided to inflate the brain and make the details larger. They did this by adding the same absorbent material found in diapers to thin slices of mouse brain that had different types of tissues dyed in varying colors. When they added water the brain slice swelled expanding the details.

The result: some really cool images and a tool already being used by scientists around the world. It is now called “expansion microscopy.”

Stem cell stories that caught our eye: A groove for healing hearts, model for muscular dystrophy and the ice bucket worked

Here are some stem cell stories that caught our eye this past week. Some are groundbreaking science, others are of personal interest to us, and still others are just fun.

A tight groove could help heal a heart.  We have written several posts with the theme “It takes a village to raise a stem cell.” If you want a stem cell to mature into a desired tissue you have to pay attention to all aspects of its environment—both the chemicals around it and the physical space.

A team at the Imperial College London has provided the latest chapter to this tale. It turns out if you want stem cells to consistently turn into long fibers of heart muscle, besides providing them with the right chemical signals making them grow in long narrow grooves on lab plate also helps. They got a two-fold increase in heart muscle cells compared to stem cells grown on a flat lab plate.

They’re now trying to figure out why the etched silicon chips worked so well for generating heart muscle. The journal Biomaterials and Regenerative Medicine published the work and the web portal myScience picked up the university’s press release.

Stem cell model for muscular dystrophy. In the past, when scientists have looked at muscle samples from patients with Duchenne muscular dystrophy (DMD) to see why they have the characteristic muscle weakening, they ‘ve arrived at the scene of the crime too late. At that point, the cellular missteps had already occurred and all that is left to observe was the damage.

Healthy muscle cells express dystrophin (green), not cells from DMD patients (middle), but treated stem cells from patients do (right)

Healthy muscle cells express dystrophin (green), not cells from DMD patients (middle), but treated stem cells from patients do (right)

So, a team at Kyoto University reprogrammed a patient’s cells to create iPS type stem cells. They then used genetic cues to direct the stem cells to become muscle and watched to see how what went wrong as this process happened.

“Our model allows us to use the same genetic background to study the early stage of pathogenesis which was not possible in the past,” said first author Emi Shoji.

The research published in Scientific Reports and highlighted in a university press release picked up by MedicalXpress documented the level of inappropriate influx of calcium into the cells and showed that a specific cell surface receptor channel was to blame. That receptor will now become a target for new drug therapy for DMD pateints.

Ice bucket results.  The ALS Association raised $220 million in the past year for amyotrophic lateral sclerosis, or Lou Gehrig’s disease, by getting people to dump bucket of ice water over their heads and then make a donation. More important, in just a year a major paper funded by the proceeds of the ice bucket challenge has shown a defect in the nerves of ALS patients and shown that correcting the defect makes the cells healthier. Those are pretty fast results for science.

In a paper published in the prestigious journal Science a team at Johns Hopkins found that one protein, TDP-43, was not doing its job well. When they genetically modified stem cell from ALS patients to correct that defect the cells worked properly. YahooFinance ran a story about the challenge and the new research.

“If we are able to mimic TDP-43’s function in the human neurons of ALS patients, there’s a good chance that we could slow down progression of the disease!” said Jonathan Ling, a researcher on the team. “And that’s what we’re putting all our efforts into right now.”

Of the initial $115 million raised during the early months of the challenge, 67 percent went to research, 20 percent to patient services, and nine percent to public and professional education. Just four percent went to overhead costs of fund raising.

China says it’s cracking down on clinics. I spend a considerable amount of time suggesting callers to our agency be very cautious about considering spending large sums of money to go overseas to get unregulated and unproven stem cell treatment. So, I was pleased to read this morning’s news that China’s top health authority issued regulation to control some of the most questionable clinics.

The regulations reported in China Daily note that any treatments using stem cells for conditions other than proven uses in blood diseases would be considered experimental and could only be conducted in approved hospitals. It noted conditions touted by clinics there including epilepsy, cerebral palsy, spinal cord injury and autism.

“Only eligible hospitals can perform the practice as a clinical trial for research purpose and it must not be charged or advertised. Anyone caught breaking the rules will be punished according to the new regulation,” said Zhang Linming, a senior official of the science and technology department of the commission.

Stem cell stories that caught our eye: shutting down cancer stem cells, safer BMT, better gene therapy and a 3rd ear

Here are some stem cell stories that caught our eye this past week. Some are groundbreaking science, others are of personal interest to us, and still others are just fun.

A new route to shut down cancer stem cells. A team at Texas A&M University has discovered a specific protein’s role in keeping cancer stem cells active and shown the pathway it uses to do its dirty deed. That pathway immediately became a target for future cancer therapy.

Although not universally accepted by all cancer researchers, the theory that cancer stem cells circumvent traditional therapy and keep cancers coming back is gaining credence through studies like the current one. The Texas team looked at the protein FGF that has been implicated in cancer but has not been a target of drug research because it is involved in so much of normal cell processes. It has seemed impossible to halt its bad behavior without inhibiting its good behavior. They tracked down its impact on cells believed to be cancer stem cells and found the pathway it uses for that effect. So, future teams can target this pathway rather than FGF itself and its many roles.

“If we understand how to keep these cells dormant it means that although we may have to live with the presence of cancer stem cells, we can prevent them from causing the cancer to come back,” said one of the study lead authors, Fen Wang. “That’s what we are trying to understand. That is the future of cancer therapy.”

The NewsMedical web portal picked up the university’s release about the research published in The Journal of Biological Chemistry.  CIRM funds several teams trying to thwart cancer stem cells both in blood cancers and in solid tumors.

 

Safer bone marrow transplant. The most common stem cell therapy, commonly called bone marrow transplant, has a more than three-decade record of success treating cancer patients. As doctors have grown more comfortable with the procedure, they expanded its use beyond using a person’s own stem cells and stem cells from immunologically well-matched donors to using cells from only partially matched donors. As this has increased the number of lives saved it has also increased the number of patients put at risk for the horrible complication known as graft versus host disease (GVHD). Besides being painful and debilitating, GVHD frequently ends in death.

A team at Seattle’s Fred Hutchinson Cancer Center completed a genetic analysis of transplant patients that did and did not develop GVHD. They found a specific gene marker that increases the risk of the complication by more than 50 percent and the risk of death by 25 percent. The results should push physicians with patients who have the at-risk gene to search harder for a matching donor before they resort to a mismatched transplant.

“Our data provide new information on the role of HLA-DPB1 expression in transplantation associated risks that can be used to guide the selection of donors for future transplant recipients in order to minimize the risk of acute GVHD,” said Effie Petersdorf, one the study authors in an article in MEDPAGETODAY.

The study appears in this week’s New England Journal of Medicine, but anyone who does not want to climb the journal’s pay wall, can get considerable more detail in the MEDPAGE article written by a former colleague from my days editing a national medical magazine, Charles Bankhead. You can trust Charlie to get the story right.

 

Using evolution science to improve gene therapy. The field of gene therapy—providing a correct copy of a gene to someone born with a mutation or using a gene to deliver a desired protein—is finally starting to take off. But one of the oldest tools for getting desired genes into cells, a family of viruses called adeno-associated viruses (AAVs) has serious limitations when trying to directly deliver the gene into people. Most of us have been infected with various AAVs and developed immunity to them. So, our immune system may wipe out the virus carrying the desired payload before it can deliver its goods.

Many teams have developed various forms of AAV that help a bit; making the viruses a little less likely to be recognized. Now, a team at the Harvard Stem Cell Institute has taken a major step down that path using evolutionary science. They used existing records of how the virus has changed over time to construct surface proteins that would not be recognized by the immune systems of most people alive today. Bionity.com wrote about the research that appeared in the journal Cell Reports.

 

ear on arm jpegListen up for the week’s oddest story. An Australian performance artist who goes by the name Stelarc has worked with a team of surgeons to grow an ear on his forearm, which he intends to implant with a microphone connected to the internet so followers of his art can hear what he hears 24/7. Not surprisingly, his family is a little skeptical.

Surgeons built the main part of the ear by implanting a scaffold made from standard materials used in plastic surgery and the artist’s own cells populated it with blood vessels and other tissues. But to grow the exterior ear lobe he intends to work with a team using stem cells, which is why this story appeared in my news feed dozens of times this week.

CNN Style did one of the most thorough write-ups including a good discussion of the ethics of wasting valuable time of medical professionals, something Stelarc himself discussed. He concluded that the value grew from getting the science world and art world to intermingle and better understand each other, something that has been on our soapbox for years.

“But I’ve found there’s a lot of goodwill from people who ordinarily would not have contact with an artist, and ordinarily would not see the reason for wasting time and money and their expertise on doing something like this, and that’s heartening,” Stelarc said.

Stem cell stories that caught our eye: potentially safer cell reprogramming, hair follicle cells become nerve and liver stem cells

Here are some stem cell stories that caught our eye this past week. Some are groundbreaking science, others are of personal interest to us, and still others are just fun.

A potentially safer way to reprogram cells. Ever since then soon-to-be Nobel Prize winner Shinya Yamanaka showed how to reprogram adult cells to an embryonic stem cell-like state labs around the world have jumped on that band wagon. But many of their experiments have not just been using those cells but rather looking for ways to make them more efficiently and possibly safer for clinical use.

The four “Yamanaka factors” traditionally used to make what are now called induced pluripotent stem cells (iPSCs) include genes that can induce cancer. So, folks have been justifiably nervous about using cells derived from iPSCs in patients.

Today in the journal Science two different Chinese teams report slightly different methods of using only chemicals to reprogram skin cells directly into nerves. One team worked at the Shanghai Institutes for Biological Sciences and the other worked at Peking University.

“In comparison with using transgenic reprogramming factors, the small molecules that are used in this chemical approach are cell permeable; cost-effective; and easy to synthesize, preserve, and standardize; and their effects can be reversible,” Hongkui Deng of the Peking team said in a press release used to write a piece in the International Business Times.

 

Stem cells in hair follicles may repair nerve. The base of our hair follicles contains skin stem cells as you would expect, but it also contains cells with markers suggesting they come from the area of the embryo known as the neural crest. A team at the University of Newcastle in the U.K. tested those cells to see if they have stem cell properties and they do.

They were able to use those cells to create Schwann cells, support cells that our bodies use to repair nerves and help with certain systems like sensation. The team’s Schwann cells interacted with nerve cells in lab dishes the way natural cells do in the body.

“We observed that the bulge, a region within hair follicles, contains skin stem cells that are intermixed with cells derived from the neural crest – a tissue known to give rise to Schwann cells,” said Maya Sieber-Blum, in a university press release picked up by Yahoo. “This observation raised the question whether these neural crest-derived cells are also stem cells and whether they could be used to generate Schwann cells.”

They showed that the cells can indeed become Schwann cells. The researchers now want to see if their cells can repair nerve damage in an animal model.

Prior work at Stanford had turned embryonic stem cells into liver cells.

Prior work at Stanford had turned embryonic stem cells into liver cells.

Drink up. Liver stem cells found. The liver creates new liver cells quite readily, whether damaged by alcohol or other factors. But no one has known exactly where the new cells come from, with most researchers assuming the remaining health cells divide to create new tissue. But a team at Stanford suggested that the liver works too hard for that to be the case. In order to remove all the toxins that come its way adult liver cells have amplified certain chromosomes, and team leader Roel Nusse said that would make them unable to divide and create new cells.

So, his team set out to track down previously elusive liver stem cells. They bred mice that had cells that would have a green florescent glow if they carried a protein usually found only on stem cells. They indeed did find stem cells and tracked them as the animals matured and saw them both divide to create more stem cells and mature into adult liver cells.

“We’ve solved a very old problem,” said Nusse, who is a Howard Hughes investigator. “We’ve shown that like other tissues that need to replace lost cells, the liver has stem cells that both proliferate and give rise to mature cells, even in the absence of injury or disease.”

The Hughes Institute issued a press release and the International Business Times wrote the story and illustrated it with a photo from CIRM’s Flickr site.

Going back to figure out how the embryo makes muscles led team to way to mass produce muscle fibers

Sometimes in science what seems like the simpler task turns out to be the hardest. We have written extensively about research teams building mini-organs in lab dishes turning stem cells into multiple layers of tissues organized and functioning, at least in part, like the kidney, liver or stomach they mimic. Given these successes and the relative simplicity of our muscles, you would have thought we would have petri dishes with bulging biceps by now. We don’t. But a team at Harvard and Brigham and Women’s hospital has made a major stride toward that goal.

Smooth muscle cells grown from embryonic stem cells (courtesy Sanford-Burnham Institute).

Smooth muscle cells grown from embryonic stem cells (courtesy Sanford-Burnham Institute).

While previous work has created small amounts of short muscle fibers from stem cells, the Brigham group created large quantities of millimeter-long muscle fibers. This level of muscle development could produce therapeutic quantities of new muscle that would be needed to treat patients with muscular dystrophy. This goal has sent many teams back to the lab looking for better ways to direct stem cells to become muscle.

The current work, published this week in Nature Biotechnology, went back to the basics and tried to understand each step that a stem cell goes through on the way to becoming muscle in the embryo. Medical Daily wrote a piece on the work, and used a quote in the Brigham press release from the senior author Olivier Pourquie:

“We analyzed each stage of early development and generated cell lines that glowed green when they reached each stage. Going step by step, we managed to mimic each stage of development and coax cells toward muscle cell fate.”

Stem cell scientist often find that going back to learn and mimic the natural steps of development works better than guessing what factors are most important in a cell’s fate. Now that they hold a map to the path between stem cell and muscle fibers, they can use it to study many different muscle diseases and work toward therapies for those often-untreatable conditions.

“This has been the missing piece: the ability to produce muscle cells in the lab could give us the ability to test out new treatments and tackle a spectrum of muscle diseases,” Pourquie said.

CIRM funds a dozen projects working to understand and develop therapies for muscle disease.

Stem cell stories that caught our eye: Prostate cancer and BPA, mini organs and diabetes trial

Here are some stem cell stories that caught our eye this past week. Some are groundbreaking science, others are of personal interest to us, and still others are just fun.

Latest mini-organ, a prostate, fingers BPA. A team at the University of Illinois, at Chicago, has added the prostate gland to the growing list of “organoids” that have been grown from stem cells in the lab. The tiny gland that produces semen in men has an unusually high rate of cancer compared to other organs. Prior research has linked that cancerous nature to exposure to the hormone estrogen during fetal growth, including synthetic estrogen mimics like the chemical BPA (bisphenol A) found in many plastics.

Unlike the other organs associated with male gender, which form very early in fetal development, the prostate develops later when stem cells’ roles are more narrowly defined to creating specific tissues. The team, led by Gail Prins, had previously shown that prostate stem cells grown in the presence of BPA formed cells more likely to show signs of cancer. But that did not allow them to determine what really triggered the increase in cancer. So, they decided to grow mini prostates and look at all the cells as they developed in the organoid.

“What we were doing originally with the human prostate stem cells is we were mixing and growing them in vivo,” Prins told Medical Daily. “The idea to generate this organoid came from the first author, Esther Calderon-Gierszal; she was my graduate student. ‘They’ve done it for other organs,’ she thought. ‘Let’s try it for a prostate.’”

The researchers pushed embryonic stem cells to grow into the several different tissues found in a prostate gland using a cocktail of hormones. Although much smaller than a normal prostate the cells did self-organize into structures that resembled the gland. When they grew the organoid in the presence of BPA they found an unusually large number of prostate specific stem cells. So, it appears just the increased number of stem cells increases the likelihood a few will go bad and form cancer.

A round up of all the mini-organs. The journal Nature has written a very accessible wrap up in its news section on all the various organs that have been simulated in a lab dish since a Japanese team reported the phenomenon for the first time in 2008. After a fun lead-in explaining the science, Cassandra Willyard runs through what has been accomplished so far in the stomach, kidney, and liver.

Part of a miniature stomach grown in the lab, stained to reveal various cells found in normal human stomachs [Credit: Kyle McCracken]

Part of a miniature stomach grown in the lab, stained to reveal various cells found in normal human stomachs [Credit: Kyle McCracken]

The fun in the opening section comes from the fact that given the right environment, stem cells are pretty darn good at self-organizing into the multiple tissue types that become a specific organ. So much so, that the early teams that saw it in the lab were shocked and did not at first know what they had.

Willyard starts with quotes from Madeline Lancaster, a post-doctoral fellow in a lab at the Institute for Molecular Biotechnology in Vienna, Austria. She found milky looking spheres in the lab cultures and when she cut into them she found multiple types of nerves. So she grabbed her mentor and reported:

“I’ve got something amazing. You’ve got to see it.”

She also discusses the work that led Hans Clevers, a researcher at Hubrecht Institute in Utrecht, the Netherlands, to report the creation of mini-guts in 20009. They grew the cells in a gel that resembled the structure that naturally surrounds cells. In this “at-home” environment stem cells formed much more complex tissue than he had hoped.

“The structures, to our total astonishment, looked like real guts,” Clevers said. “They were beautiful.”

The author also lets Clevers talk about taking his work the next step, using the gut organoids to screen for drugs for related diseases. If you have been following this work, Willyard’s piece is a must read.

Second clinical trial site for diabetes. Opening multiple clinical trial sites accelerates the process of determining whether a new therapy is safe and effective. So we were thrilled to get the announcement from ViaCyte that they would begin enrolling patients at a second location for the diabetes trial we helped them launch by funding the first clinical trial site at the University of California, San Diego.

That trial uses pancreatic cells grown from embryonic stem cells that are protected from immune attack by a semi-permeable pouch. The second site, at the University of Alberta Hospitals in Edmonton, Canada, is being funded in part by Alberta Innovates as well as by the JDRF Canadian Clinical Trials Network. JDRF also helps support the San Diego trial through its US office.

The lead researcher for the Alberta trial, James Shapiro, developed the procedure for transplanting pancreatic tissue from cadavers that became known as “the Edmonton Protocol.” That protocol has changed many lives, but because it requires life-long immunosuppression, doctors only recommend it for the most severe diabetics. The small number of donor pancreases also limits its use. Shapiro commented about the value and need for something like the ViaCyte therapy in a company press release picked up by Yahoo Finance, and dozens of other sites:

“The fact remains that new treatments are sorely needed, not only for the high risk patients but for all patients suffering from this life-altering disease.  The remarkable promise of the (ViaCyte) product candidate is that a virtually limitless source of appropriate human cells can be transplanted without the need for lifetime immunosuppression.”

Global stem cell market predicted to reach $40 billion in five years, even bigger when mixed with new technologies

The global consulting firm Frost and Sullivan held a webinar yesterday in which they noted health care systems everywhere are facing an increasing challenge of costly chronic care. They suggested health care providers have started to embrace regenerative medicine as a viable alternative.

Because of its power to change the course of disease, the consultants called regenerative medicine, and stem cell therapies in particular, a new paradigm in human health.

“Regenerative Medicine initiatives are now attracting new public and private funding,” said the firm’s Jane Andrews in a widely picked up press release, including this post at CNBC. “Although Stem Cell Therapy will continue to be the largest market segment of Regenerative Medicine, cross segment therapies that combine the use of immunology, genetic and stem cell therapy are rapidly advancing,”

CIRM funds projects in all these technologies so it is always nice to see others joining the fight. We recently posted a series of stories about our portfolio of clinical trials that combine cell therapy and gene therapy.

The report predicts the global stem cell therapy market will reach $40 billion in five years by 2020. It also suggests that just the US market will reach $180 billion by 2030.

The firm does raise a cautionary note about the inadequacy of funding for early stage clinical work with these therapies. Our President and CEO Randall Mills has also raised an alarm about this issue and called on industry to increase its support for this work.

Organized by the Asia-Pacific branch of Frost and Sullivan the webinar breaks out the markets for Japan, Korea and Singapore. The webinar itself is available on line.

Cranking up stem cell production for when therapies are approved for widespread use

Getting a cell therapy from the research bench to patients requires leaping many hurdles. Perhaps two of the highest arise when proving the potential therapy is safe enough to begin clinical trials and then when scaling up production to meet the demand of thousands of patients.

Scale up to producing the 100s of billions of cells needed to treat large groups of patients could be a roadblock for therapies.

Scale up to producing the 100s of billions of cells needed to treat large groups of patients could be a roadblock for therapies.

An even dozen CIRM-funded projects have made it over the first hurdle. No doubt those teams have begun planning for that last big jump, but in reality, in most cases the processes needed to make cells for a dozen or a few dozen patients in early trials don’t generally scale to the thousands. When you look at the number of cells needed for one heart repair, for example, around five billion, the numbers are mind bending.

Many organizations focus on this issue as their main goal looking for platforms that can help scale up production for cell therapies across many different diseases. A team at the University of Nottingham in England recently reported results from a $3.6 million project that seems to have created a sizeable piece of the solution. They developed a fully synthetic substrate, which has no chance for contamination, that can grow cells by the billion, both stem cells and the more mature cells normally desired for transplant into patients.

“The possibilities for regenerative medicine are still being researched in the form of clinical trials,” said the project leader Morgan Alexander in a university press release posted by ScienceDaily. “What we are doing here is paving the way for the manufacture of stem cells in large numbers when those therapies are proved to be safe and effective.”

The research team used a high throughput lab technique to test many materials until they finally arrived at the one they reported in the journal Advance Materials.

Stem cell stories that caught our eye: fixing defects we got from mom, lung repair and staunching chronic nerve pain

Here are some stem cell stories that caught our eye this past week. Some are groundbreaking science, others are of personal interest to us, and still others are just fun.

Two ways to clean up mitochondrial defects. Every student gets it drilled into them that we get half our genes from mom and half from dad, but that is not quite right. Mom’s egg contains a few genes outside the nucleus in the so-called powerhouse of the cell, the mitochondria that we inherit only from mom. The 13 little genes in that tiny organelle that are responsible for energy use can wreak havoc when they are mutated. Now, a multi-center team working in Oregon and California has developed two different ways to create stem cells that match the DNA of specific patients in everyway except those defective mitochondrial genes.

The various mitochondrial mutations tend to impact one body system more than others. The end goal for the current research is to turn those stem cells into healthy tissue that can be transplanted into the area most impacted by the disease in a specific patient. That remains some years away, but this is a huge step in providing therapies for this group of diseases.

Currently, we have two ways of making stem cells that match the DNA of a patient, which hopefully result in transplantable cells that can avoid immune rejection. One is to reprogram adult tissue into induced pluripotent (iPS type) stem cells and the other uses the techniques called Somatic Cell Nuclear Transfer (SCNT), often called therapeutic cloning. The current research did both.

The team converted the SCNT stem cells into various needed tissues such as these nerve precursor cells.

The team converted the SCNT stem cells into various needed tissues such as these nerve precursor cells.

The iPS work relied on the fact that our tissues are mosaics because of the way mitochondria get passed on when cells divide. So not all cells show mitochondrial mutations in people with “mito disease” —how impacted families tend to refer to it, as I found out through a distant cousin with a child valiantly struggling with one form of the disease. Because each iPS stem cell line arises from one cell, the researchers could do DNA analysis on each cell line and sort for ones with few or no mutations, resulting in healthy stem cells, which could become healthy transplant tissue.

But for some patients, there are just too many mutations. For those the researchers inserted the DNA from the patient into a healthy donor egg containing healthy mitochondria using SCNT. The result: again healthy stem cells.

“To families with a loved one born with a mitochondrial disease waiting for a cure, today we can say that a cure is on the horizon,” explained co-senior author Shoukhrat Mitalipov at the Oregon Stem Cell Center in a story in Genetic Engineering News. “This critical first step toward treating these diseases using gene therapy will put us on the path to curing them and unlike unmatched tissue or organ donations, combined gene and cell therapy will allow us to create the patients’ own healthy tissue that will not be rejected by their bodies.”

ScienceDaily ran the Oregon press release, HealthCanal ran the press release from the Salk Institute in La Jolla home of the other co-senior author Juan Carlos Izpisua Belmonte, whose lab CIRM funds for other projects. And Reuters predictably did a piece with a bit more focus on the controversy around cloning. Nature published the research paper on Wednesday.

Stem cells to heal damaged lungs. Lung doctors dealing with emphysema, cystic fibrosis and other lung damage may soon take a page from the playbook of cancer doctors who transplant bone marrow stem cells. A team at Israel’s Weizmann Institute has tested a similar procedure in mice with damaged lungs and saw improved lung function

Transplanted lung cells continued to grow at six weeks (left) and 16 weeks (right).

Transplanted lung cells continued to grow at six weeks (left) and 16 weeks (right).

Stem cells are homebodies. They tend to hang out in their own special compartments we call the stem cell niche, and if infused elsewhere in the body will return home to the niche. Bone marrow transplants make use of that tendency in two ways. Doctors wipe out the stem cells in the niche so that there is room there when stem cells previously harvested from the patient or donor cells are infused after therapy.

The Weizmann team did this in the lungs by developing a method to clear out the lung stem cell niche and isolating a source of stem cells capable of generating new lung tissue that could be infused. They now need to perfect both parts of the procedure. ScienceDaily ran the institute’s press release.

Stem cells for chronic pain due to nerve damage. Neuropathy, damaged nerves caused by diabetes, chemotherapy or injury tends to cause pain that resists treatment. A team at Duke University in North Carolina has shown that while a routine pain pill might provide relief for a few hours, a single injection of stem cells provided relief for four to five weeks—in mice.

They used a type of stem cell found in bone marrow known to have anti-inflammatory properties called Bone Marrow Stromal Cells (BMSCs). They infused the cells directly into the spinal cavity in mice that had induced nerve damage. They found that one chemical released by the stem cells, TGF Beta1, was present in the spinal fluid of the treated animals at higher than normal levels. This finding becomes a target for further research to engineer the BMSCs so that they might be even better at relieving pain. ScienceNewsline picked up the Duke press release about the research published in the Journal of Clinical Investigation.

Giving stem cells the right physical cues produced micro hearts, maybe a tool to avoid birth defects

Heart defects, one of the leading types of birth defects, often result from drugs mom is taking, but we have not had a good model of developing fetal hearts to test drugs for these side effects. Now, a team at the University of California, Berkeley and the Gladstone Institutes has created micro heart chambers in a lab dish by providing the starting stem cells with the right physical cues. And they found these mini-hearts can predict birth defects.

Different types of cells required to make functioning heart tissue show up as different colors here.

Different types of cells required to make functioning heart tissue show up as different colors here.

As we have written before, it takes a neighborhood to raise a stem cell into a wanted adult cell. While most lab cultures maturing stem cells into adult tissue are flat, the developing fetal heart grows in an environment with many physical cues, both chemical and pressure. The Berkeley team added a chemical layer to the cell culture dish and etched it to provide added physical cues. The result produced both connective tissue and heart muscle that were organized into micro heart chambers that could beat.

“We believe it is the first example illustrating the process of a developing human heart chamber in vitro,” said Kevin Healy, co-senior author of the study at UC Berkeley. “This technology could help us quickly screen for drugs likely to generate cardiac birth defects, and guide decisions about which drugs are dangerous during pregnancy.”

The team took the added step of testing a drug known to cause birth defects, thalidomide. When the stem cells were growing with the drug added to the culture, they did not develop into the same micro chambers.

The Berkeley bioengineers started with stem cells reprogrammed from adult skin tissue in the CIRM-funded lab of Bruce Conklin at the Gladstone, the other co-senior author on the paper. These iPS-type stem cells were essential to the project.

“The fact that we used patient-derived human pluripotent stem cells in our work represents a sea change in the field,” said Healy. “Previous studies of cardiac micro-tissues primarily used harvested rat cardiomyocytes, which is an imperfect model for human disease.”

 

Berkeley issued a press release on the work and Popular Science wrote a piece on it complete with a fun embedded video of the beating tissue. The journal Nature Communication ran the original research publication today.