Cells derived from embryonic stem cells, iPS cells appear immature

A trend over the past few years has been comparing embryonic stem cells, adult stem cells and reprogrammed adult cells (also known as iPS cells) to each other and to other cell types. The goal is to understand what the cells are, exactly, and and how they differ from each other. Eventually this information could help researchers learn which type of cell will be most effective for developing therapies, understanding diseases or drug screening.

A group of CIRM grantees at UCLA has published the latest in the unfolding story of stem cell comparisons. In their case, they didn't compare the stem cells themselves. Instead, they matured embryonic stem cells and iPS cells into the cells that eventually form neurons, cells that eventually form skin, and cells that eventually form liver. These so-called progenitor cells also exist in adult humans, where they lurk in tissues waiting to be needed to repair damage.

The scientists compared the progenitor cells to each other and to equivalent cells taken from adult tissue as well as to developing tissues. What they found is that the progenitors for nerves, skin and liver that came from embryonic or iPS cells had a lot in common with each other and with developing tissues. However, they had much less in common with their counterparts taken from adult tissues.

A press release from UCLA quotes William Lowry, who was senior author on the paper, which appeared in Cell Research.

“What we found, looking at gene expression, was that the cells we derived were similar to cells found in early fetal development and were functionally much more immature than cells taken from human tissue. This finding may lead to exciting new ways to study early human development, but it also may present a challenge for transplantation, because the cells you end up with are not something that’s indicative of a cell you’d find in an adult or even in a newborn baby.”

The release goes on to quote first author Michaela Patterson:

“One important reason to do this is to ensure that the cells we are creating in the Petri dish and potentially using for transplantation are truly analogous to the cells originally found in humans,” said Michaela Patterson, first author of the study and a graduate student researcher. “Ideally, they should be a similar as possible.”

…

“The roles these cells play in the fetus and the adult are inherently different,” she said. “It may be that the progeny, if transplanted into a human, would mature to the same levels as those found in the adult liver. We don’t know.”

This is the first paper we've seen comparing progenitor cells to adult or developing tissues. As with all first steps, we'll likely see more papers over the next few years refining and expanding on this team's findings and clarifying what these findings mean in terms of transplantation.

CIRM Funding: William Lowry (RS1-00259-1), Michaela Patterson (T1-00005)
Cell Research, August 16, 2011

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Stem cells improve brain function after radiation therapy

CIRM grantees at University of California Irvine have used human neural stem cells to help alleviate brain damage that occurs after radiation to treat brain tumors.

Radiation can be an effective way of treating tumors in the brain, but the radiation also kills surrounding healthy tissue in addition to the destroying the tumor. Even if the cancer is eliminated the person can be left with debilitating learning and memory loss. A press release from UCI quotes senior author on the work Charles Limoli, who has a CIRM SEED award to carry out this work:

“In almost every instance, people experience severe cognitive impairment that’s progressive and debilitating,” Limoli said. “Pediatric cancer patients can experience a drop of up to three IQ points per year.”

Limoli and his team wanted to know if the brain's stem cells could repair that damage. They injected human neural stem cells into the brains of rats that had undergone radiation treatment. Those stem cells migrated to the damaged part of the brain and matured into nerves and the brain's support cells. The release quotes Limoli:

“This research suggests that stem cell therapies may one day be implemented in the clinic to provide relief to patients suffering from cognitive impairments incurred as a result of their cancer treatments,” Limoli said. “While much work remains, a clinical trial analyzing the safety of such approaches may be possible within a few years, most likely with patients afflicted with glioblastoma multiforme, a particularly aggressive and deadly form of brain cancer.”

If their work is successful, this technique could help people live normal lives after being treated for brain cancers. That would be good news for individuals, their caregivers and for the state, which loses tax income when people are unable to work or must decrease work to care for family members.

Cancer Research, July 15, 2011
CIRM Funding: Charles Limoli (RS1-00413-1)

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CIRM grantee Robert Blelloch wins ISSCR Outstanding Young Investigator Award

CIRM grantee Robert Blelloch of the University of California, San Francisco won the 2011 Outstanding Young Investigator Award from the International Society for Stem Cell Research. The society's annual meeting is taking place now in Toronto.

Blelloch presented his research June 15 at 6pm and will participate in a press briefing at noon June 16. His work focuses on the role of small molecules called microRNAs and their role in stem cell biology and cancer.

Jennifer O'Brien described Blelloch's work in a press release from UCSF:

During the last few years, Blelloch’s team has reported several key findings. In 2008, they reported that microRNAs promote self renewal of embryonic stem cells in mice (Nature Genetics, 2008). In 2009, they showed that when those same microRNAs were inserted into adult cells the cells de-differentiated back into embryonic stem cells (Nature Biotechnology, 2009). In 2010, they inserted a microRNA into embryonic stem cells and promoted differentiation, but determined that the microRNA had to compete with microRNAs that promote embryonic stem cell self-renewal (Nature, 2010). This year, his laboratory has been looking at microRNAs as a potential tool to systematically dissect the molecular pathways that regulate cell fate transitions, including dedifferentiation of adult cells to create induced pluripotent stem cells (Nature Biotechnology, 2011).

“People have come to realize microRNAs are remarkably powerful,” said Blelloch, associate professor in the Departments of Urology, Obstetrics, Gynecology and Reproductive Sciences and Pathology and a member of the Helen Diller Family Comprehensive Cancer Center.

Using microRNAs for therapeutic purposes has great potential , he said. “They could be used either to induce adult cells to de-differentiate to embryonic stem cells, which could be expanded, manipulated and returned to a patient, or to promote differentiation of embryonic stem cells to produce tissues that would remain integrated in the body once re-introduced.” They also could be used to target cancers, and they attract interest from biotechnology companies.

Blelloch has a SEED Award and a New Faculty II Award, both looking at the role of microRNAs in embryonic stem cell biology. Not to blow our own horn, but CIRM does know how to pick high quality research. Last year Stanford's Joanna Wysocka won the same award. She has a SEED Award and a New Faculty I Award from CIRM.

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Techniques for tracking stem cells necessary for possible therapies

Last week The Scientist carried a story addressing a topic near and dear to the heart of anyone trying to develop a therapy based on transplanting stem cells, whether they are embryonic, adult, or iPS cells: Where do the cells go once they are transplanted?

The problem is this — if you, as a scientist, transplant stem cells near some damage that you are hoping they will repair, you've got to hope those cells actually make it to the damaged tissue. If they make a run for the liver when you are trying to treat the heart, or simply sit in a lump where you implanted them, those cells aren't going to fulfill their mission.

The story quotes CIRM grantee Joseph Wu of Stanford University who has SEED and Basic Biology III Awards to detect stem cells implanted into the heart and to develop stem cell transplantation therapies for hypertrophic cardiomyopathy.

“If you want to understand what happens to these stem cells, it’s important to track the fate of these cells without having to kill the animal,” says Joseph Wu, a cardiologist at Stanford University School of Medicine in Palo Alto, California. Stem cell transplants may settle down, proliferate, and differentiate as desired; they may form dangerous tumors; or they may simply falter and die.

The issue is also one CIRM grantee Paul Knoepfler of the University of California, Davis, touched on in his blog last week, saying:

Once these cells, which have spent weeks in a lab environment, are injected into a person, what happens next?

This is arguably the most important question in the regenerative medicine field, but there are few answers. We are literally mostly in the dark about what cells do after transplant, but there are some things that can be predicted pretty confidently.

He goes on to discuss some of what's known about the issue using Geron's clinical trial as an example.

In their article, the Scientist discusses a few techniques scientists are using (including some nice images) to address the question of where the cells go. The story includes a technique being used by CIRM grantee Eduardo Marban at Cedars-Sinai Medical Institute, who has a Disease Team Award to develop a therapy for heart disease.

This is the type of research that comes to mind when people who don't follow the science comment on the lack of cures. CIRM is funding a broad range of science, some of which is primarily dedicated developing new therapies, and some of which is working to understand these kinds of basic questions that need to be addressed before those therapies can become widespread.

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Celebrating National Cancer Research Month with a cancer stem cell round-up

In celebration of National Cancer Research Month, our colleagues at Sanford-Burnham Medical Research Institute have posted a series of blog entries about cancer research at their institute. The latest installment includes CIRM grantee Robert Wechsler-Reya, who moved to California from Duke University on a CIRM Research Leadership Award.

According to their blog:

Dr. Robert Wechsler-Reya, who directs the Tumor Development Program in Sanford-Burnham’s Cancer Center, has spent many years studying how “good” processes can also cause disease. He is particularly interested in how mechanisms that are normal in embryonic development can cause cancer when turned on in children and adults.

“We work on the relationship between development and cancer, particularly in the brain,” says Dr. Wechsler-Reya. “We’re interested in how normal stem cells and progenitor cells make decisions like when to divide, when to differentiate and what to differentiate into. We’re interested in how those decisions go wrong in cancer.”

To-date, CIRM has awarded more than $130 million to cancer research, including grantees working to understand the role of cancer stem cells in the disease and other teams working to develop therapies. Among our Disease Team projects, which have the goal of reaching clinical trials by 2014, CIRM funded two teams working on therapies for glioma (City of Hope and UCSF), two working on therapies for leukemia (Stanford and UCSD), and one working on solid tumors (UCLA).

Here are a few resources CIRM offers for people trying to get information about stem cells and cancer.

• Information about stem cells and glioma
• Information about stem cells and leukemia
• Information about stem cells and solid tumors

We also produced this video with CIRM grantee Catriona Jamieson at Moore's UCSD Cancer Center at the University of California, San Diego. Jamieson has a therapy in clinical trial for a pre-cancerous blood condition. The work that led to that trial was funded in part by a CIRM SEED grant.



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How a stem cell forms a neuron

CIRM grantees at Sanford-Burnham have published another paper using an embryonic stem cell model to understand one of the earliest steps in human nervous system development. (We've blogged about their work before here.)

The group led by Alexey Terskikh has been trying to understand how a group of cells called the neural crest form nerves, skin, bone and muscle. This process has been somewhat mysterious because it happens at such an early stage in development. Scientists can't exactly peer into a woman's womb to see the process unfold.

That's where embryonic stem cells come in. These cells can form all cell types in the body, including neural crest. On their blog, Sanford-Burnham quotes first author on the May 5 Cell Stem Cell study Flavio Cimadamore:

“Neural crest cells are notoriously difficult to study in humans because of their very early and transient nature – a woman is usually not even yet aware of her pregnancy when they start to migrate and differentiate. So here we took advantage of an embryonic stem cell-based model of human neural crest previously developed in our lab to get a better understanding of the molecular pathways that control the differentiation potential of such cells in humans.”

In the current work, the team found that neural crest cells with a gene called SOX2 turned on can go on to form neurons. Those without it can't. That's critical information for people who are trying to understand diseases that arise from neural crest cells that go awry during development. Microphthalmia and CHARGE syndrome are two rare but debilitating childhood diseases that could benefit from knowing more about how the neural crest normally develops.

In the blog entry, Terskikh said:

"We hope this finding will be useful to researchers studying neural crest development and stem cell differentiation.”

CIRM funding: Alexey Turskikh (RS1-004661); Flavio Cimadamore (TG2-01162)
Cell Stem Cell, May 5

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Making neurons lose their inhibitions

CIRM grantees at Sanford-Burnham have just published an interesting paper in PLoS Biology about developing a type of neuron that could alleviate symptoms of Huntington's disease, autism, schizophrenia and bipolar disorder — all diseases in which some neurons lose their inhibitions.

First, the big picture. In the brain, some neurons send signals to other neurons, relaying information around the brain. Others simply act to dial up or down those signals. A group of neurons in a part of the brain called the basal ganglia serve to dial back signals from other parts of the brain, basically keeping the signals under control.

In some neurological diseases, it's the loss of those inhibitory neurons that allow signals to run rampant and cause symptoms. In which case, adding some new inhibitory neurons might be what it takes to control symptoms.

What postdoctoral fellow Christina Chatzi knew is that some inhibitory neurons rely on a molecule called retinoic acid in order to develop properly. Retinoic acid is a form of vitamin A that has long been known to aid in developing limbs and body patterning. Working in the lab of Gregg Duester, Chatzi wondered if exposing embryonic stem cells to retinoic acid could result in these inhibitory neurons. Turns out she was right.

Duester's lab studies the basic biology of the role of retinoic acid in development, but they say others may want to follow up on this work in attempt to develop therapies. Sanford-Burnham's excellent blog entry quotes Duester:

"But what we found here suggests that others could use retinoic acid to make inhibitory neurons to treat disease, just the way an embryo does it naturally."

This work is one great example of how basic biology can feed into the development of new therapies -- something we've blogged about before. Without a constant source of new ideas going into the research pipeline there will be no cures coming out the other end.

CIRM funds two awards to scientists working toward therapies involving inhibitory neurons derived from embryonic stem cells: A comprehensive award to Arnold Kriegstein at the University of California San Francisco, and an Early Translational II award to Arturo Alvarez-Buylla also at UCSF.

- A.A.

CIRM funding: Gregg Duester (RS1-00193)
PLoS Biology, April 12, 2011

Legal wrangling slows Stanford researcher's quest for a cure

Joanna Wysocka/Stanford University

What does all the legal wrangling mean for stem cell scientists? Stanford published a profile of up-and-coming star Joanna Wysocka, who talks about her own NIH-funded research. Wysocka was awarded the Outstanding Young Investigator Award at the annual meeting of the International Society for Stem Cell Research in June and has both a SEED and a New Faculty award from CIRM. In her acceptance speech for the ISSCR award Wysocka credited her SEED award for pulling her into the field of stem cell research.

Amidst her other successes, Wysocka also received the highest of scores on an NIH grant proposal that would fund stem cell research with the promise to help children with a rare developmental disorder known as CHARGE syndrome, which leads to life-threatening complications.

That award is one of the ones that got held up in the Aug. 23 ruling that threw NIH funding of human embryonic stem cell research into a tailspin. The Stanford story says:

“I am currently funding this project largely from leftovers of my start-up funds and relatively unrestricted junior investigator awards, but we need more money to continue,” she said. While the latest ruling means that the NIH can fund grants like hers, there is uncertainty among researchers nationwide due to the unsettled state of the law.

As of September 9, the NIH can once again proceed with funding human embryonic stem cell grants, but that funding is far from settled. That uncertainty could lead to significant delays.

Although the NIH now can move forward on her grant, she’s not sure how fast it can act — and whether the next court ruling could deal another setback before that happens. She noted that the NIH committee that must give final approval for her funding met while Lamberth’s ruling was in effect, so it did not consider her grant. That committee meets only three times a year, she said, so now she may have to wait.

“The review process was disrupted — it’s not something that can change in a day,” she said. “I have no clue when my grant will get back on track.”

The stem cell researchers and people employed in their labs are disrupted by the legal back and forth, but what’s worse is the uncertainty for families of children with CHARGE syndrome who look to work like Wysocka’s with hope.

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iPS cells from women create model for muscular dystrophy, X-linked diseases

Reprogrammed skin cells showing inactivated X in red

CIRM grantees at the University of California, Los Angeles have uncovered a feature of reprogrammed iPS cells that make them uniquely excellent for understanding diseases that arise from mutations on the X chromosome.

First some background. Men inherit an X chromosome from their mother, which contains many thousands of genes, and a Y from the father, which does little except confer manhood. Women inherit one X chromosome from each parent. Those female cells overcome their genetic overabundance by shutting down, at random, one of the two X chromosomes, putting the cells at genetic par with male cells.

But the two aren’t really equal. If men inherit a mutation on an X chromosome, it is present in every cell of the body and can cause muscular dystrophy, Rett Syndrome, color-blindness and other disorders. Women who inherit a mutation on an X chromosome from one parent will only show that mutation in half their cells. The other half of the body's cells, with the non-mutated chromosome active, can generally compensate.

So what does this have to do with reprogrammed cells and disease modeling? It turns out that the process of reprogramming skin cells into embryonic-like induced pluripotent stem cells doesn’t overturn the inactivated X. Reprogramming cells from a woman’s skin sample will produce two distinct types of iPS cell lines; half with one X active, and half of with the other X active. If one of those two chromosomes carries a mutation, say, for muscular dystrophy, some of those iPS lines will also display that mutation.

In a press release from UCLA, senior author Kathrin Plath said:

“This non-random pattern of X chromosome inactivation found in iPS cell lines has critical implications for clinical applications and disease modeling and could be exploited for a unique form of gene therapy for X-linked diseases.”

In a publication in Cell Stem Cell, Plath and her colleagues report that they created iPS cell lines from a woman who had inherited one X chromosome carrying a mutation that can cause muscular dystrophy. The other X chromosome had a normal copy of the gene. Scientists can now mature both groups of cells into skeletal muscle and compare the resulting tissue as a way of understanding—and perhaps one day treating—the devastating disease.

Cell Stem Cell: September 3, 2010
CIRM funding: Sean Sherman (TG2-01169), Kathrin Plath (RN1-00564), William Lowry (RS1-00259), Jerome Zack. (RL1-00681)

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)

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Neural stem cells reverse Alzheimer's symptoms in mice

Researchers at the University of California, Irvine have reversed Alzheimer’s-like symptoms in a mouse model of the disease with injections of neural stem cells. The mice used in this study mimicked the human disease, showing learning and memory defects and accumulating both beta-amyloid plaques and tau protein tangles within the brain, the two hallmark pathologies of the disease.  Mice that received injections of mouse neural stem cells performed significantly better in memory tests than mice that received control injections. The stem cells did not replace cells lost to the disease. Instead, the injected cells secreted a protein known as brain-derived neurotrophic factor (BDNF), that helped nourish the surviving neurons, encouraging those cells to grow more fibers and form more connections. The injected cells did not reduce the plaques or tangles. Current therapies for Alzheimer’s disease can only reduce the severity of symptoms or slow progression. To date, this is only the second potential treatment shown to actually improve memory in mice with advanced plaque and tangle pathology.



Proceedings of the National Academy of Sciences, August 11, 2009
CIRM funding: Frank LaFerla (RS1-00247-1), Matthew Blurton-Jones (T1-00008)

Related Information: UCI Press Release, University of California, Irvine, LaFerla bio

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Protein required to maintain full potential of stem cells

Researchers at the University of California, San Francisco have pinpointed a protein that is critical for maintaining a stem cell’s full potential to self-renew and to differentiate. Stem cells lacking the protein were impaired in their ability to divide and make identical copies of themselves, called self-renewal. These cells also lost their capacity to differentiate into key cell types, such as cardiac muscle. The protein, Chd1, acts to keep chromosome strands loosely wound, which permits widespread gene activation in the cell’s nucleus. Previous studies hypothesized that this open chromosome structure is necessary in stem cells to maintain their potential to specialize into any cell type. Additional results in this study demonstrate that Chd1 is required for efficient reprogramming of adult cells, such as skin cells, back into a pluripotent state. These new insights into Chd1 function may lead to safer, more efficient methods for growing up large numbers of embryonic stem cells and deriving specific cell types, both critical steps for successful stem cell therapeutic strategies.

Nature, July 8, 2009 (online publication)
CIRM funding: Rupa Sridharan (T1-00002), Kathrin Plath (RN1-00564-1), Miguel Ramalho-Santos (RS1-00434-1)

Related Information: press release, University of California, San Francisco

Genetic differences found between adult cell and embryonic-derived stem cells

Researchers at the University of California, Los Angeles have found genetic differences that distinguish induced pluripotent stem (iPS) cells from embryonic stem cells. These differences diminish over time, but never disappear entirely. iPS cells are created when adult cells, such as those from the skin, are reprogrammed to look and behave like embryonic stem cells. But until now, scientists didn’t know if the two types of stem cells were actually identical at a molecular level. This latest research shows that iPS and embryonic stem cells differ in which genes they have turned on or off. All early iPS cells share these genetic traits, regardless of what animal they come from, the type of adult cells the iPS cells start as, or what method was used to reprogram those adult cells. However, later cultures of iPS cells show that most, but not all, of these differences disappear over time, making later cultures of iPS cells more similar to embryonic stem cells. If scientists want to use iPS cells in medical therapies, this research will give them a better idea of how similar they are to embryonic stem cells.

Cell Stem Cell: July 2, 2009
CIRM funding: Mike Teitell (RS1-00313), Kathrin Plath (RN1-00564-1), William Lowry (RS1-00259-1, RL1-00681-1)

Related Information: Press Release, University of California, Los Angeles

Embryonic stem cells repair nerve damage from mutiple sclerosis in mice

Researchers at the University of California, Irvine have found that neurons derived from  embryonic stem cells were able to repair some damage in a mouse model of multiple sclerosis. In people with MS, the immune system attacks the insulation – called myelin – that covers and protects neurons of the brain and spinal cord. The transplanted cells caused a response in the animals that allowed the myelin coating to be repaired on damaged cells. In humans, repairing the myelin would likely also repair the function of those nerves, bringing back feeling and motor control in people with MS. At this time there are no therapies to repair this damage. Instead, available drugs simply slow the progression of the disease. In this early study, the transplanted neurons survived only two weeks. The authors say more work is needed to understand how the remyelination occurred and how to retain the transplanted cells.

Journal of Neuroimmunology: May 23, 2009 (online)
CIRM funding: Chris Shaumberg (T1-00008), Thomas Lane (RS1-0409)

Related Information: University of California, Irvine

Genetic molecule enables safer method for creating iPS cells

Researchers at the University of California, San Francisco have designed a safer technique for reprogramming adult cells into a state that resembles embryonic stem cells. This method takes advantage of genetic molecules called microRNAs, which regulate the activity of genes. The original 2007 method for creating reprogrammed cells, called induced pluripotent stem (iPS) cells, relied on inserting four genes, some potentially tumor-causing, into the DNA of an adult cell such as a skin cell. Since then, researchers have whittled the number of genes down to two, and in one case generated iPS cells with only chemicals. However, the process is often inefficient. In this study, the researchers substituted one of the four genes with a microRNA molecule and obtained iPS cells at high efficiency. The researchers suggest microRNAs could replace other genes or improve the efficiency of chemical means of creating iPS cells. In addition, understanding how microRNAs function in reprogramming could lead to new therapeutic strategies for blocking reprogramming in cancer stem cells.



Nature Biotechnology, April 12, 2009
CIRM funding: Robert Blelloch (RS1-00161)

Related Information: Press release, University of California, San Francisco

iPS Cells Mature into Functional Motor Neurons

Researchers at the University of California, Los Angeles have matured induced pluripotent stem (iPS) cells into what appear to be normal motor neurons. This work shows that iPS cells can mature into cells that appear similar to those derived from human embryonic stem cells – a finding that has important implications for people hoping to create new therapies based on iPS cells. These cells are created by reprogramming adult cells back into a pluripotent state that resembles embryonic stem cells. One question has been whether these reprogrammed cells have the same capacity as embryonic stem cells to turn into mature, functioning cell types. This work shows that, at least for motor neurons, iPS and embryonic stem cells have the same capacity to form mature cells. Scientists can study these motor neurons in the lab to learn about – and find cures for – diseases such as amyotrophic lateral sclerosis (Lou Gehrig’s Disease), spinal muscle atrophy or spinal cord injury.

Stem Cells:February 23, 2009 (online publication)
CIRM funding: William Lowry (RS1-00259)

Related Information: Broad Stem Cell Research Center, Lowry lab page

Neural Cells Can Mature into Ear Sensory Cells

Researchers at the University of California, Davis have coaxed cells from the brain to mature into the minute hair cells in the ear that are required for hearing. For many people with hearing loss, these tiny hair cells have died, leaving people unable to sense vibrations caused by sound. Regrowing functional hair cells that will sway in response to sound and send appropriate signals to the brain has been a major goal for stem cell researchers. In this work, the team found a population of cells in the lateral ventricle of the brain that they were able to transform into the delicate hair cells. The team is now testing whether those cells are able to transmit sound signals in animal models.

Proceedings of the National Academy of Sciences: December 30, 2008
CIRM funding: Dongguang Wei (T1-00006), Ebenezer Yamoah (RS1-00453)

Related Information: Press Release, UC Davis Health Care System, Yamoah bio

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

Embryonic stem cells repair heart damage in mice

Researchers at the Stanford University School of Medicine found that cells derived from human embryonic stem cells could repair damage in a mouse model of heart attack. The researchers first looked at which genes were active at every stage between the human embryonic stem cells and early heart muscle cells. The cells they implanted mirrored the genes that are active in the hearts of 20 week old fetal mice. After injecting the cells into the heart of a mouse with an induced heart attack, they found that the cells incorporated into the heart and significantly improved the heart’s ability to pump blood. This work could lead to new stem cell-based therapies for repairing damaged heart tissue

PLoS ONE: October 22, 2008
CIRM funding: Joseph Wu (RS1-00322)

Related Information: Stanford Stem Cell Biology and Regenerative Medicine Institute, Wu bio

First clinical Trial Begins for a Therapy Enabled By CIRM Funding

Researchers at UC, San Diego verified a suspect gene mutation in blood-forming stem cells was by itself necessary and sufficient to cause a class of severe blood diseases called myeloproliferative disorders. They then worked with a team of researchers from other academic institutions and from the San Diego pharmaceutical company TargeGen to conduct animal tests of a compound TargeGen had already isolated and shown to inhibit that same genetic pathway. As a result of this broad collaboration, human clinical trials for this potential therapy began in February, 2008.



CIRM funding: Catriona Jamieson

Related Information: UC San Diego press release, UCSD Stem Cell Initiative