Of salamanders, mice and men - digit regeneration mechanisms revealed

Regenerated mouse digit tip/Yuval Rinkevich

 Guest blogger Uta Grieshammer is a science officer at CIRM

A form of regeneration that has captured the imagination of scientists and the general public for many decades occurs in certain salamanders, as they have the remarkable ability to regrow a severed leg. Leg regeneration is unusual not only because it is so rare among vertebrates, but also because the underlying mechanism is thought to be quite different from that operating during the regeneration of organs in mammals.

Although mammalian legs do not regenerate, the very tips of our fingers and toes, and those of mice, do sometimes regrow. A new study published August 24 in Nature from Irv Weissman’s lab at Stanford University, and partially funded by CIRM, now comes to the surprising conclusion that the mechanism at work during mouse digit tip regeneration more resembles that of our other organs rather than the way that salamanders’ legs have been thought to regrow.

Although it may not be obvious, many of the organs in a healthy person regenerate themselves throughout life, some more than others. Our whole blood forming system and our gut, for instance, turn over relatively rapidly, whereas only about half of our heart cells are replaced in our entire life. Some organs, such as our skin, muscles, and bones, also have a reasonable capacity for repair after injury, if the damage was relatively small, while much of our liver will be faithfully replaced after a large portion has been removed. Other organs, though, replace cells lost to insult or disease only poorly or not at all, such as the heart following a heart attack. The hope is, if we figure out how the regeneration superstars of our body, or those of salamanders, accomplish their remarkable feats, we can use that knowledge to coax their less talented brethren into action.

Scientists have three basic models for how regeneration occurs: 1) tissue-specific stem cells within the organ divide and mature into the additional tissue, 2) mature cells divide to produce more of themselves without contributing to other cell types, or 3) mature cells lose their specificity, become more like embryonic cells and form a blastema with the ability to divide and form the original cell type and also other cell types in the regenerating tissue.

Weissman’s work with postdoctoral scholar Yuval Rinkevich, who was first author on the paper, shows that during digit regeneration in mice, the third model is not the right one. Remaining skin cells only make new skin cells, bone cells only make new bone. This comes a bit as a surprise, as this appears to be very different from the blastema mechanism thought to be used by salamanders to regrow their limbs. However, recent experiments from Elly Tanaka’s group in Dresden have challenged that long held model, showing that blastema cells in regrowing salamander legs do not typically adopt fates different from those of the cells they’re derived from. These studies then suggest that regeneration of limbs and digits in salamanders and mice, respectively, does occur through related mechanisms, just not the one originally thought. In both cases, repopulating cells do not switch cell fate, but whether regenerated digit or limb cells are derived from tissue-specific stem cells or from mature cells remains an open question for both species, although the Weissman paper makes a cogent argument that their data are consistent with the stem cell model, at least for some of the cell types involved in mouse digit regeneration.

Concerted efforts by scientists studying animals such as salamanders and mice will likely lead to an ever more accurate picture of limb and digit regeneration, thereby laying the groundwork for translating these findings to human cells, and eventually to human treatments.

CIRM funding: Irv Weissman (RC1-00354)
Nature, August 24, 2011

Genes at the heart of heart deformities found through stem cell studies

CIRM grantees at The Gladstone Institutes have, over the past few years, been hard at work learning about the origins of heart deformities by studying how stem cells mature into heart tissue.

What they've learned is that small relatives of DNA, called micro-RNAs, help control when and how cells mature into heart tissue (blogged about here and here) or blood vessels (blogged about here). In recent work out of the lab of Deepak Srivastava, they also discovered three genes are activated by a key micro-RNA whose absence can lead to heart deformities. That work is published in the April 17 Developmental Cell.

The work was in fruit flies, but many basic discoveries in fruit flies directly translate to humans.

Isabelle King, who works with Srivastava at the Gladstone Institutes and led the study, said discovering those genes could help scientists understand and treat cases where the heart failed to form properly in development. A press release from Gladstone quotes King:

“In the fetal heart, subtle changes in gene dosage and timing can yield heart defects in children.”

This work is a great example of how basic stem cell research can lead to new areas to explore for disease therapies. People often think of stem cell therapies as exclusively transplantation therapies in which stem cells and their derivatives are transplanted into a diseased organ to restore function. We do fund scientists trying to do just that, but we also fund basic stem cell scientists who are discovering how diseases arise, and the genes responsible. These discoveries made possible by studying stem cells could lead to new drugs or other interventions that have nothing to do with transplantation.

On the topic of basic research, we'll be funding our third round of Basic Biology Awards at our governing board meeting next week (here are review summaries of those applications). These awards are intended to foster the kinds of basic stem cell and disease discoveries that keep new ideas — and eventual cures — flowing.


Developmental Cell, April 17, 2011
CIRM funding: Deepak Srivastava (RC1-00142); Li Quan (TG2-01160)

Stem cell model of autism allows testing of new drugs

Back in May 2009, CIRM held a workshop in which leading scientists discussed ways in which stem cell research could benefit people with autism (here is the autism workshop report from that meeting). I have two friends with children who are on the spectrum and have seen first-hand the toll the disease takes on the families.

This week, some CIRM grantees published an exciting paper that reflects the hopes of that workshop. The scientists took skin cells from people with a severe form of autism called Rhett syndrome, reverted those cells to an embryonic state, and matured them into neurons. The work was published in the in the November 11 issue of Cell. This is the first time scientists have been able to study what amount to autistic neurons in a lab dish.

It turns out they have some abnormalities, as you might expect. According to Technology Review:

They found that neurons derived from patients with Rett syndrome showed certain abnormalities, including markedly smaller cell bodies, dendrite connections, and decreased cell-to-cell communication.

The best part is that when the team from the Salk Institute and the University of California, San Diego exposed these neurons to a protein called insulin-like growth factor the neurons looked more normal.

This type of work is precisely what the workshop recommended as a starting point. Nerves grown from people with autism are an ideal environment for testing possible therapies and for understanding the disease. The group hopes to test therapeutic options suggested by these findings in mice, and to grow neurons from people with different forms of autism.

At this point the work is far too early to benefit my friends. The scientists still need to better understand the different forms of autism, study this proposed therapy in animals and understand the mechanism better before they can even begin thinking about a human trial. But for a disease that currently has so little clinical hope, even early stage work is a step in the right direction.

CIRM funding:
Fred Gage (RL1-00649-1 and RC1-00115-1)

Stem cell research like picking stocks? We don't think so.

A story by Nick Wade in Monday’s New York Times rubbed some scientists the wrong way — and I must admit the piece was not too popular around CIRM headquarters.

Wade equated research funding with picking stocks. His idea is that a broad portfolio is bound to include some winners (he attributes this approach to the NIH and NSF) whereas attempts to only buy the big winners can produce a risky portfolio (an approach he attributes to CIRM).

Writing for the science portal Science 2.0, Michael White writes:

This is not right.* Wade goes astray in thinking of science in terms of hits and misses. Basic research is not like being at bat, with the occasional single base hit or home run being the exception in a sea of strikeouts.

Most research is simply conventional and incremental. Most of the time it's not a miss, a disaster, or a failure - it's a small, sometimes not too surprising addition to our knowledge of a subject. Most research projects and NIH grants end in success, not failure - but the successes are usually small. In fact, there probably aren't enough failures, because, unlike the venture capitalists Wade compares it to, the NIH is very unwilling to take risks in search of the spectacular winner. Funded projects are the ones almost guaranteed to work.

CIRM grantee Paul Knoepfler at UC Davis also takes objection to the piece. His point: CIRM isn’t just investing in one big thing. Three billion dollars to just fund one area of stem cell research, that would be narrow. But CIRM has funded an incredible range of research, from the most basic science to translational work, and in approaches spanning stem cell transplantation therapies to modeling disease, drug testing, and models of regeneration (the very research Wade suggests we should fund).

Knoepfler writes:

Clearly [Wade] knows very little about CIRM and about stem cell research. He makes the argument that because CIRM only funds research in 'a single field' that chances are high that Californians will lose out. First, he is wrong that CIRM only funds one field. The breadth of research funded by CIRM spans a few dozen fields from cancer biology to neurological disorders, to heart disease, diabetes, HIV/AIDS, etc. Second, Mr. Wade ignores the substantial accomplishments that CIRM has already made in just its first few years.

Where CIRM agrees with Wade’s piece is in his suggestion that we look to how animals such as zebrafish and newts naturally regenerate, and use that knowledge to improve human regeneration. Deepak Srivastava from the Gladstone Institutes, who has been looking at tissue regeneration in mouse hearts, is making tremendous progress in part through CIRM funding (here is his research summary), as is USC’s Gage Crump, studying zebrafish jaw regeneration as a model for bone regeneration (here is his research summary). 

For people interested in seeing the range of what CIRM has funded, we have this searchable list of all our funded stem cell research awards. We also have this list of our rounds of funding, explaining the role that funding plays in creating CIRM’s broad research portfolio.

A.A.

Embryonic No More

CIRM grantees at UCLA have captured the first moment when an embryonic stem cell – it of infinite possibilities – chooses a more limited fate.

A press release from UCLA says the cell population (which the researchers dubbed human embryonic mesodermal progenitors, or hEMP cells) could be therapeutically useful. The cells still have broad ability to become bone, blood, muscle or blood vessels, but – and this is an important but – have lost the embryonic stem cell’s propensity to form tumors called teratomas.

Gay Crooks, a professor of pathology and laboratory medicine and senior author of the study, is quoted in the release as saying:

“The hEMP cells we isolated did not have the ability to make teratomas, so they should be a safer choice when thinking about developing therapies for use in humans.”

In addition to being useful in developing therapies, the cells are just plain cool. Scientists don’t know what it is that gives an embryonic stem cell the freedom to choose its fate (a state called pluripotency). Crooks puts it like this:

“We want to know what it is that switches on and off to make a pluripotent cell no longer be pluripotent. In this study, we found a cell population that can help us understand these processes, as it is such a close relative to embryonic stem cells, but has lost the ability to be pluripotent.”

What they learn could help colleagues who are looking for more efficient ways of reprogramming adult cells to become pluripotent iPS cells.

PNAS, July 19, 2010
CIRM Funding: Gay Crooks (RC1-00108-1)

A.A.

Between Mice and Men, a New Type of Stem Cell

Humans and other non-human primates stand out from their fellow mammals in many ways, but notably by having one particularly oversized area of the brain. This area, the outer subventricular zone (OSVZ) feeds migrating neurons to the neocortex the seat of sensory perception, spatial reasoning, conscious thought and language. Scientists always assumed the OSVZ must have its own source of stem cells if, in the developing brain, it is supplying neurons for such a broadly vital area of the human brain. They have now found them.

Arnold Kriegstein’s team at UCSF used discarded fetal tissue to monitor cellular activity at various stages of development using a new labeling and tracking technique. They found the OSVZ to be a hub of cell proliferation. The newly found stem cell type goes through asymmetrical division producing a copy of itself and a daughter cell that is further along the path to becoming a neuron. That cell then goes through many rounds of symmetrical division producing many copies that can all then go on to become the desired neuronal cells needed in the neocortex.

A press release issued by UCSF on May 24 noted that the understanding provided by this model could shed light on many developmental brain diseases such as autism and schizophrenia. Kreigstein is quoted saying this understanding is critical:

“If we’re going to understand how these disorders develop, we have to better understand how the human and primate cerebral cortex develops.”

Understanding this developmental pathway will also inform efforts to direct neural stem cells to become the replacement cells of choice for various therapies.

D.G.

Nature, March 25 2010
CIRM Funding: Arnold Kriegstein (RC1-00346-1), Jan Lui (T1-00002)

Hairs in a Dish Give Hope to Damaged Ears

The microscopic hair cells found in the inner ear are so sensitive to vibration they can relay to the brain whether the air movement around them is from guitar licks by Eric Clapton or a piano chord from a Chopin Palinais, but too many loud Metallica concerts can damage them leading to hearing loss. Now, a team of stem cell scientists at Sanford has succeeded for the first time in growing these sensory cells from embryonic or iPS cells in a laboratory dish (shown in the image, taken in the laboratory of Stefen Heller at Stanford University), a key step in understanding how they really work and to growing new cells to replace damaged ones.

The team lead by Stanford’s Stefan Heller coaxed mouse embryonic stem cells in a dish into maturing into cells that looked and acted like the animal’s inner-ear hair cells. A press release from the university quoted Harvard neuroscientist David Corey, who was not connected to the study, offering hope and calling for patience:

“This gives us real hope that there might be some kind of therapy for regenerating hair cells. It could take a decade or more, but it is a possibility.”

The researchers accomplished this feat with both embryonic stem cells and stem cells created by reprogramming skin cells, so called iPS cells. They used various growth factors to first coax embryonic or iPS cells into becoming ectoderm, the embryo’s outer layer, then coaxed those ectoderm cells into progenitor cells for the ear and then into the hair cells.

Heller works on two paths toward curing deafness: drug therapy to resurrect the malfunctioning hair cells and stem cell-derived cell transplants. His team’s hairy dish could speed work for both. In the release he said:

“We could now test thousands of drugs in a culture dish. It is impossible to achieve such a scale in animals.”

It's exciting to see how far this research has come since 2008, when CIRM hosted a Spotlight on Deafness, with talks by clinicians, researchers, and a deaf woman eager explaining why she's hopeful for a cure.

Cell, May 14, 2010
CIRM Funding: Stefan Heller (RC1-00119-1)

D.G.

Engineered human stem cells destroy HIV infected cells

A group at the University of California, Los Angeles AIDS Institute has manipulated human blood-forming stem cells to fight HIV infected cells. The technique could conceivably be used to help the body fight any number of viral infections, the authors say.

The researchers started with blood-forming stem cells normally found in the bone marrow. These cells form all the cells of the human blood system including immune and red blood cells. They then inserted a gene from an immune cell of an HIV-infected individual. That protein can recognize the HIV virus and would ordinarily guide the person’s immune system to attack infected cells. In an HIV-infected person so few of those infection-fighting cells exist that the immune system can’t do its job. 

The idea was that blood-forming stem cells carrying that HIV-targeting protein would mature into an immune system primed to recognize and destroy HIV-infected cells.

To test their idea, the authors inserted the engineered stem cells into mice. These mice also had transplanted into them a human thymus, the organ that is responsible for making a population of infection-fighting cells called T cells. (The human T cells can’t mature properly in the mouse thymus. By implanting the mouse with a human thymus the researchers mimicked how the cells might behave in a human.) As they hoped, the blood-forming stem cells produced  human T cells that were able to kill HIV-infected cells.

The authors called this study a proof-of-principle, saying that by inserting different proteins into the blood-forming stem cells they could direct the immune system to attack Hepatitis, herpes or human papillomavirus.

A press release by UCLA quotes Jerome Zack, an author on the paper and CIRM grantee, as saying:

"This approach could be used to combat a variety of chronic viral diseases. It's like a genetic vaccine."

PLoS ONE, December 7, 2009
CIRM funding: Jerome Zack (RC1-00149)

A.A.

Embryonic stem cells repair radiation damage in mice

Radiation can effectively destroy brain tumor cells – but at a cost. While killing the tumor cells the treatment also damages normal cells in portions of the brain involved in learning and memory, leaving people with varying levels of impairment. New work by researchers at the University of California, Irvine suggests that human embryonic stem cells are able to ameliorate radiation-induced normal tissue damage.

The group, led by CIRM SEED grantee Charles Limoli, irradiated the heads of rats then transplanted human embryonic stem cells into the brain. In a memory test four months after the radiation, transplanted rats performed as well as rats that had never been irradiated. Rats that received radiation but no transplanted stem cells showed a significant decline in learning and memory.

The transplanted cells had migrated through the brain and matured into a variety of brain cells. The cells did not form any tumors (at least by 4 months) – something scientists are careful to watch for in transplanted stem cells.

In a press release by UCI, Limoli said:

"With further research, stem cells may one day be used to manage a variety of adverse conditions associated with radiotherapy."

Proceedings of the National Academy of Science: November 10, 2009
CIRM funding: Charles Limoli (RS1-00413-1), Peter Donovan (RC1-00110-1)

A.A.

Molecules found that control the development of blood vessel cells

Researchers at the Gladstone Institute of Cardiovascular Disease have identified two molecules, called microRNAs, that push early heart cells to mature into the smooth muscle cells that line blood vessels. These same molecules also control when those smooth muscle cells divide to repair damage or in diseases such as cancer or atherosclerosis, which both involve unhealthy blood vessel growth. The two microRNAs, miR-145 and miR-143, are abundant in the primitive heart cells of prenatal mice, leading those cells to differentiate into various mature heart and aorta cells. After birth, both microRNAs are present mainly in smooth muscle cells, which also line the small intestine. If both microRNAs are absent, smooth muscle cells in blood vessels start multiplying. This helps heal injured blood vessels, but it can also create abnormal blood vessel growth in certain diseases. This cell proliferation can thicken blood vessels in atherosclerosis, or it can nourish tumors with blood. These findings could help scientists create smooth muscle cells from embryonic stem cells for therapeutic uses, or could lead to therapies for atherosclerosis or cancer.

Nature, July 5, 2009 (online publication)
CIRM funding: Deepak Srivastava (RC1-00142-1), Kathy Ivey (T2-00003)

Related Information: Press Release, Gladstone Institute of Cardiovascular Disease, Srivastava bio

Protein protects brain from damage, may prevent neurodegenerative diseases

Researchers at the University of California, San Diego and the Salk Institute for Biological Studies have found a protein that protects the brain from the kind of damage that can lead to Parkinson's disease. This protein, called Nurr1, has a long history in Parkinson's disease research. People who carry a mutation in the gene are prone to developing the disease. The new work explains how the protein prevents Parkinson's disease and could also help researchers find ways of treating of preventing the disease. The protein was especially important in two types of cells that protect and support the brain's neurons -- called microglia and astrocytes. In these cells, Nurr1 works with other proteins to limit inflammation after an immune response. Without it, these support cells produced toxic by-products that damaged the nerves in a way that could lead to Parkinson's disease or other neurodegenerative diseases.

Cell: April 3, 2009
CIRM funding: Beate Winner and Fred H. Gage (RC1-00115), Christian Carson (T3-00007), Leah Boyer (T1-00003)

Related Information: Press release, University of California, San Diego, Salk Institute for Biological Studies, Gage bio

Support Cells Prevent Mature Heart from Repairing Damage

Researchers at the Gladstone Institute of Cardiovascular Disease may have discovered why developing heart muscles cells multiply in numbers while the adult counterparts do not. This finding could lead to therapies that roll back the clocks on heart muscle cells after injury such as a heart attack, allowing those cells to multiply and repair the damage. The researchers specifically looked at the role of cells called fibroblasts, which are packed in the heart amidst the muscle cells. They found that fibroblasts in embryonic mouse hearts release proteins that encourage the muscle cells to divide. In contrast, fibroblasts in adult hearts release proteins that encourage muscle cells to expand in size but actively inhibit the cells from multiplying. That role makes sense in healthy hearts, where new cells aren’t needed, but after injury those fibroblasts prevent the heart from being able to repair itself. The researchers hope this finding could lead to new ways of repairing heart tissue after injury.

Developmental Cell: February 16, 2009
CIRM funding: Deepak Srivastava (RC1-00142), Kathy Ivey (T2-00003)

Related Information: Press Release, Gladstone Institute of Cardiovascular Disease, Srivastava bio

Embryonic Stem Cells Generate Model for ALS

Researchers at the Salk Institute for Biological Sciences have grown embryonic stem cells into the motor neurons and support cells that underlie amyotrophic lateral sclerosis (ALS). Also known as Lou Gherig’s Disease, ALS has no cure and no effective treatment. In this disease, the motor neurons slowly degenerate leaving a person paralyzed. Why the neurons die is not known, however the support cells called astrocytes have long appeared to play a role. Now researchers have coaxed embryonic stem cells to form the motor neurons and astrocytes in a lab dish to better understand their relationship in ALS. What they learned is that astrocytes containing a mutation associated with ALS killed off the neighboring motor neurons. This mutation is in a gene that makes a protein whose normal role is to protect the body from damaging oxygen free radicals. When the group grew these same cells in the presence of a powerful anti-oxidant, the motor neurons survived. In addition to understanding the biology of ALS, the group thinks they could use this system to screen drugs that may be able to treat ALS.



Cell Stem Cell: December 4, 2008
CIRM funding: Fred H. Gage (RC1-00115)

Related Information:Press release, Salk Institute for Biological Sciences, Gage  bio

Genetic Factor Enables Immature Cells to Form Normal Heart Tissue

Researchers at the Gladstone Institute for Cardiovascular Disease found a genetic factor that helps in the earliest stages of heart development as the primitive tube loops around on itself and forms the separate chambers. This factor -- a short relative of DNA called microRNA -- has an identical counterpart in humans, leading the researchers to believe that their work in fish is likely to relate directly to human heart development. When the researchers interfered with this microRNA while the heart was developing, the immature heart muscle cells failed to mature and the heart chambers didn’t form normally. These heart muscle precursors are a stage in between the embryonic stem cell and the mature heart muscle cell. The heart is among the first organs to develop and also the most critical. When the heart doesn’t develop properly the embryo dies. What’s more, common birth defects involve abnormalities in how these chambers form. Understanding all the steps between an embryonic stem cell and the mature heart cell could help researchers prevent or treat birth defects of the heart.

Proceedings of the National Academy of Sciences: November 12, 2008
CIRM funding: Kathy Ivey (T2-00003), Deepak Srivastava (RC1-00142)

Related Information: Press release, Gladstone Institute of  Cardiovascular Disease, Srivastava bio

Protein found to direct embryonic stem cells as they mature

Researchers at the Stanford University School of Medicine have found that clusters of embryonic stem cells in a lab dish share some unexpected similarities with actual embryos. These clumps, called embryoid bodies, consist of hundreds of cells, many of which begin to form more mature cell types. For example, they often contain groups of primitive heart muscle cells that beat visibly. In this work the researchers found that the embryoid bodies also contain a line of cells that resemble an embryonic structure called the primitive streak. This streak is the first indication that the embryo has a top and bottom or back and front. Blocking molecules found in the embryoid body primitive streak pushed those cells to form a group of cells that make up skin and nerves. Enhancing those molecules pushed the cells to form cell types like muscle and intestine. This work could help researchers learn how to push embryonic stem cells to form particular cell types, which is a necessary step in developing stem cell-based therapies.

Cell Stem Cell: November 6, 2008
CIRM funding: Roel Nusse (RC1-00133-1)

Related Information: Press release, Stanford Stem Cell Biology and Regenerative  Medicine Institute, Nusse lab page

Early immune cells created from embryonic stem cells

Researchers at UC, Los Angeles have created cells that go on to form normal T cells out of human embryonic stem cells. What’s more, these cells were grown in the absence of animal feeder cells, which are usually needed to sustain embryonic stem cells. Avoiding potential contamination by such feeder cells is an important step in generating cells that can be transplanted into people. The researchers describe a series of steps that drive human embryonic stem cells to begin developing as T cells. When they transplanted the cells into mice with human thymus tissue, where T cells normally mature, those cells did mature into normal adult T cells. In addition, the group inserted genes into their immature T cells before transplantation and saw evidence that those genes were active in the mature, transplanted cells. This work brings researchers closer to creating cells that can be transplanted into people as a therapy for disorders of the immune system, including HIV/AIDS.

Stem Cells: October 30, 2008 (online publcation)
CIRM funding: Zoran Galic (RS1-00203), Aparna Subramaniana (T1-00005), Jerome Zack (RC1-00149)

Related Information: The Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at UCLA , Zack bio

New Stem Cell Lines Created from Testes Biopsy

Researchers at Stanford University School of Medicine have created new stem cell lines from cells found in the human testes. Like embryonic stem cells, these cell lines are pluripotent, which means that they can form all cell types in the adult body. The work follows similar research finding that adult stem cells in mouse testes can be reprogrammed into pluripotent cells. However, the researchers found that the cells differed from embryonic stem cells in several important ways. This is in contrast to a recent paper in Nature finding that the testes-derived stem cells are equivalent to their embryonic counterparts. The researchers suggest that different conditions in the lab may create cells that are more similar to truly pluripotent embryonic cells. Despite the differences, these reprogrammed stem cells cells could be a source of new sperm in men who become infertile due to chemotherapy. They could also one day become a source of stem cells for patient-specific transplants.

Stem Cells: October 16, 2009 (online publication)
CIRM funding: Renee Reijo Pera (RC1-00137)

Related Information: Press Release, Stanford Stem Cell Biology and Regenerative Medicine Institute, Pera bio

New Embryonic Stem Cell Lines Avoid Animal Products

Researchers at Stanford University School of Medicine derived new human embryonic stem cell lines using minimal animal products. Although numerous groups have derived stem cell lines, most were generated in the presence of animal serum and animal-derived feeder cells. These animal products are a concern because they may cause the stem cells to produce an immune response when transplanted into humans and may induce biological changes especially to the genome. In this study, the team characterized six lines that were derived with minimal use of animal products.  The researchers verified that the lines behave like normal ES cells in their ability to both self-renew and differentiate to the major cell types.  These lines may be useful for future studies that help move the field toward clinical-grade cell therapy.

Stem Cells and Development: June 17, 2008
CIRM funding: Renee Reijo Pera (RC1-00137)

Related Information: Stanford Stem Cell Biology and  Regenerative Medicine Institute, Pera lab page

Method Produces Nerve Cells More Quickly

Researchers at the Burnham Institute for Medical Research have developed a new way of quickly maturing embryonic stem cells into neural cells. Other research groups have worked out lab conditions that encourage embryonic stem cells to mature into various types of nerve cells, but those methods were slow and resulted in early stage nerve cells that were more likely to cause tumors when transplanted into mice. This new method could speed work by researchers who are trying to develop therapies for diseases of the nervous system. As an additional benefit, this work showed that some previously overlooked genes are worth studying as potential regulators of embryonic stem cell maturation.

Cell Death and Differentiation: March 13, 2009
CIRM authors: R Bajpai (T2-00004), Stuart Lipton (RC1-00125), Alexi Terskikh (RS1-00466)

Related Information: Press release, Burnham Institute for Medical Research, Lipton bio, Terskikh bio

Genetic Factor Influences Heart Muscle Formation from Embryonic Stem Cells

Researchers at the Gladstone Institute for Cardiovascular Disease discovered how two specific tiny genetic factors called microRNAs influence the differentiation of embryonic stem cells into heart muscle. They found that the factors not only drive the versatile cells to become heart, but also actively prevent them from becoming other tissue such as bone adding to their potential to make therapy more specific and targeted for patients.

Cell Stem Cell: March 6, 2008
CIRM funding: Kathey Ivey (T2-00003), E. Hsiao (T2-00003), Deepak Srivastava (RC1-00142)

Related Information: Press release, Gladstone Institute of  Cardiovascular Disease,Srivastava bio