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