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

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

Origin of blood stem cells found to be in the lining of blood vessels

Researchers at UC, Los Angeles have found that blood-forming stem cells in mice have their origins in the endothelial cells that line blood vessels during mid-gestation. These cells eventually move to the bone marrow where they generate all the cells of the blood system throughout life. Researchers have long known that blood-forming stem cells arise from the blood vessels, but didn’t know exactly which cell type acted as the source. Now that the source is know, the researchers want to learn what signals those endothelial cells to begin producing blood-forming stem cells. This information could eventually help researchers learn how to create those stem cells in the lab and maintain the cells in the stem cell state rather than forming mature cell types. Currently, it isn’t possible to grow blood stem cells in large quantity in the lab. Having a source of these cells would be useful for bone marrow transplants to treat cancer or for research purposes.

Cell Stem Cell: December 4, 2008
CIRM funding: Ann Zovein (T1-00005)

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

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

Genetic Factors Found to Speed Embryonic Stem Cell Division

Researchers at UC, San Francisco developed a novel way of finding out the role of DNA-relatives called microRNA. These molecules are known to turn genes on and off and appear to regulate whether embryonic stem cells remain as stem cells or develop into mature cell types, but learning which genes are controlled by each microRNA has been a challenge. Using this screen, the researchers found 14 microRNAs that speed up cell division; of those, five are commonly found in human embryonic stem cells. It turns out these microRNAs deactivate genes that slow the cell cycle, essentially releasing the brakes on cell division. Identifying the role of these and other microRNAs could help researchers understand how to hold embryonic stem cells in their immature state, guide how those cells mature, or even develop treatments for cancer.

Nature Genetics: November 2, 2008
CIRM funding: Yangming Wang (T1-00002)

Related Information: Press release, UCSF Institute for Regeneration Medicine, Blelloch 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

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

Genetic Profile Distinguishes Types of Stem Cells

Researchers at the The Scripps Research Institute found a new way of classifying the many cell types that fall under the category of “stem cells.” The term stem cell refers to tissue specific stem cells found in mature tissues such as blood, brain, or muscle, which are restricted to forming only cells found in those tissues, as well as to embryonic stem cells that are broadly able to form all cells of the body. The term is also used to refer to the so-called induced pluripotent stem (iPS) cells that scientists can now create out of adult skin cell and that mimic embryonic stem cells in their ability to form a variety of cell types. In this work, the researchers discovered a set of genes that are always active in the pluripotent cells – whether they were iPS cells or embryonic stem cells. As more stem cell populations become available, the gene profile discovered in this study will help researchers distinguish those cells that are truly pluripotent from those that are more restricted in the cell types they are able to form.

Nature: September 18, 2008
CIRM funding: Louise Laurent (T1-00003)

Related Information: Scripps news story, The Scripps Research Institute

Human Embryonic Stem Cells Trigger Immune Reaction in Mice

Researchers at the Stanford University School of Medicine have found that human embryonic stem cells trigger an immune response much like organ rejection when transplanted into mice. In the past, researchers had thought that transplanted embryonic stem cells might not be rejected the way transplanted organs are. Testing this theory, the team found that after transplanting human embryonic stem cells into normal mice, those cells disappeared within seven to ten days. In mice without an immune system the cells survived and even multiplied. Drugs used to prevent organ rejection also successfully prevented normal mice from rejecting the transplanted stem cells. These results suggest that any therapy involving transplanted embryonic stem cells will also require a way of preventing people from rejecting those therapeutic cells.

Proceedings of the National Academy of Sciences: September 2, 2008
CIRM funding: Joseph Wu (RS1-00322)

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

True Location of Brain Stem Cells Discovered

Researchers at UC, Irvine identified the true location of adult stem cells in the brain. Previous studies indicated that in mammals, adult neural stem cells originate in a region of the brain called the subventricular zone. In this study, the team found evidence that stem cells exist only in a region called the ependymal layer, which is adjacent to the subventricular zone. They also coaxed the ependymal stem cells to divide in adult rats displaying Parkinson's Disease-like symptoms. This work raises the possibility that manipulating cells of the ependymal cell layer could lead to stem cell therapies for neurological diseases.

Neuroscience: July 11, 2008
CIRM funding: Darius Gleason (T1-00008)

Related Information: UC, Irvine press release, Sue and Bill Gross Stem Cell Research  Center

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

Fly Stem Cells Create their Home

Researchers at the Salk Institute of Biological Studies discovered that stem cells in the testes of fruit flies are able to generate their own support cells. This work in flies could help guide researchers hoping to understand the environment surrounding resident populations of human stem cells - called the niche. The niche is difficult to study in humans but is an area of great interest because any therapy based on transplanting stem cells into a tissue will require those cells to be paced in a niche where they will thrive. This work raises the possibility that some transplanted stem cells may be able to produce their own niche.

Nature: July 20, 2008
CIRM funding: Justin Voog (T1-00003)

Related Information: Salk press release, Salk Institute for Biological Studies

Aging Muscles Inhibit Stem Cells, Prevent Repair

Researchers at UC, Berkeley identified a signaling molecule that interferes with the ability of older skeletal muscle to regenerate. After injury, adult skeletal muscle regenerates by activating muscle stem cells that fuse with the existing muscle cells to repair the damage. This ability to regenerate diminishes with age, not because of a decline in the number of resident stem cells, but because stem cells in the older muscle don’t respond when damage occurs. It turns out that older muscles release molecules that actively inhibit the resident stem cells. In this study, the team identified one of those molecules and showed that interfering with that molecule’s function restores the ability of muscle in older mice to regenerate after injury. This research illustrates the potential for recruiting adult resident stem cells in tissue repair.

Nature: June 15, 2008.
CIRM funding: Morgan Carlson (T1-00007)

Related Information: Press release, Berkeley Stem Cell Center

Mutation Revealed to Convert Blood Stem Cells to Cancer Stem Cells

Researchers at UC, Los Angeles discovered a series of mutations that can convert normal blood stem cells into cancer stem cells. It is believed that many types of cancer result from cancer stem cells created by such mutations. In this case the first mutation converted normal stem cells and then caused over expression of an oncogene, a cancer gene, resulting in a proliferation of leukemia stem cells and acute T-cell lymphoblastic leukemia in a mouse model. The team hopes that by studying these pathways they will find ways to block them with small molecule drugs and cure the often fatal disease.

Nature: May 22, 2008
CIRM funding: Wei Guo (T1-00005)

Related Information: UCLA press release, The Eli and Edythe Broad  Center of Regenerative Medicine and Stem Cell Research at UCLA

Pattern of Small Genetic Factors Found to Characterize Embryonic Stem Cells

Researchers at The Scripps Research Institute discovered that human embryonic stem cells have a very specific signature when it comes to the regulators of their genes. MicroRNAs are very small, naturally occurring bits of genetic material. They don't code for specific proteins like genes do, but they regulate the activity of genes and turn on and off their protein production. In embryonic stem cells microRNAs are actively preventing the production of proteins that tell cells to differentiate into specific heart or bone tissue, for example, but are pushing hard on genes that result in self-renewal. The team hopes to use these microRNAs to reprogram any type of cell to become as pluripotent as embryonic stem cells and to do it more safely than current reprogramming called iPS.

Stem Cells: June, 2008
CIRM funding: Louise Laurent (T1-00003)

Related Information: Press release , The Scripps Research Institute

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

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

Validation of Technique Inducing Skin Cells to become Pluripotent Stem Cells

Researchers at UC, Los Angeles succeeded in inducing skin cells to become pluripotent cells with genetic featured very much like embryonic stem cells. They verified work published during the completion of their project, which showed that the introduction of four specific genetic factors is sufficient to induce differentiated adult cells into reverting to an embryonic stem cell-like state. This was critical validation of a procedure that could lead to a new way of developing personalized cell lines for therapy.

Proceedings of the National Academy of Sciences: February 26, 2008
CIRM funding: Rupa Sridharan (T1-00005)

Related Information: Press release, The Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA, Lowry lab page

Mutation Causing Cardiomyopathy Validated in Mouse Embryonic Stem Cells

Researchers at UC, Irvine used mouse embryonic stem cells to demonstrate that a specific mutation can cause cardiomyopathy, with a thickened heart wall, in the mouse. The team looked at the small DNA molecule located outside of the nucleus, so-called mitochondrial DNA, which we all inherit exclusively from our mothers. They also discovered that severe mutations in this mitochondrial DNA are readily eliminated from the mouse germ line in just four generations. They expect the method they used to become a robust research tool to study the impact of mutations on stem cells.

Science: February 15
CIRM-funded authors: Weiwei Fan (T1-00008), Douglas Wallace (RC1-00353)

Related Information: Press release, Sue and Bill Gross Stem Cell Research Center,