Protein Flips Switch In Embryonic Stem Cell Growth

Researchers at the Burnham Institute for Medical Research and the Scripps Research Institute have found that a protein known to play an important role in maintaining mouse embryonic stem cells has a similarly crucial job in human embryonic stem cells. This protein, called Shp2, acts as a switch, telling the cells to either divide to make more of themselves – a process called self-renewal – or to mature into different cell types – called differentiation. Fine-tuning this balance between self-renewal and differentiation will be critical for developing new therapies based on embryonic stem cells. The cells need to self-renew in order to grow up enough cells to be therapeutically useful. Once researchers have sufficient cells, they need to switch the cells over to a state where they can mature into cell types such as nerves, retinal cells, or pancreatic islets that can be used to study or treat disease.

PLoS ONE: March 17, 2009
CIRM funding: Yuhong Pang (T2-00004)

Related Information: Press Release, Burnham Institute for Medical Research

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

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

Protein in Pancreas May Lead to New Therapy for Type II Diabetes

Researchers at the Burnham Institute for Medical Research and the University of California, San Diego have found parallels between how the pancreas develops in the embryo and type II diabetes (also known as adult diabetes). When the pancreas develops in an embryo, a protein called Wnt (pronounced “wint) helps control how the cells mature into insulin-producing cells. In most adults, the pancreas contains very little Wnt protein, but in people with type II diabetes Wnt protein is abundant in the pancreas. The authors suggest that Wnt could be a target for new type II diabetes therapies.

Experimental Diabetes Research: January 20, 2009
CIRM funding: Seung-Hee Lee (T2-00004), Carla Demeterco (T2-00003)

Related Information: Press Release, Burnham Institute for Medical Research

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