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