Blocking one membrane protein can lead to large numbers of stem cells.
Experiments by researchers at the University of Pittsburgh School of Medicine and the National Institutes of Health (NIH) also show that the process doesn't require other kinds of cells or agents to artificially support cell growth and doesn't activate cancer genes.
Scientists hope lab-grown stem cells and induced pluripotent stem (iPS) cells, which have the ability to produce specialized cells such as neurons and cardiac cells, could one day be used to treat diseases and repair damaged tissues, said co-author Jeffrey S. Isenberg, M.D., associate professor, Division of Pulmonary, Allergy and Critical Care Medicine, Pitt School of Medicine.
"Even though stem cells are able to self-renew, they are quite challenging to grow in the lab," he said. "Often you have to use feeder cells or introduce viral vectors to artificially create the conditions needed for these cells to survive and thrive."
In 2008, while at NIH, Isenberg was using agents that block a membrane protein called CD47 to explore their effects on blood vessels. He noticed that when cells from the lining of the lungs, called endothelium, had been treated with a CD47 blocker, they stayed healthy and maintained their growth and function for months.
NIH researchers continued to experiment with CD47 blockade, focusing on defining the underlying molecular mechanisms that control cell growth.
They found that endothelial cells obtained from mice lacking CD47 multiplied readily and thrived in a culture dish, unlike those from control mice. Lead author Sukhbir Kaur, Ph.D., discovered that this resulted from increased expression of four genes that are regarded to be essential for formation of iPS cells. When placed into a defined growth medium, cells lacking CD47 spontaneously formed clusters characteristic of iPS cells. By then introducing various growth factors into the culture medium, these cells could be directed to become cells of other tissue types. Despite their vigorous growth, they didn't form tumors when injected into mice, a major disadvantage when using existing iPS cells.
Stem cells prepared by this new procedure should be much safer to use in patients. Also, the technique opens up opportunities to treat various illnesses by injecting a drug that stimulates patients to make more of their own stem cells.
According to Isenberg, "These experiments indicate that we can take a primary human or other mammalian cell, even a mature adult cell, and by targeting CD47 turn on its pluripotent capability. We can get brain cells, liver cells, muscle cells and more. In the short term, they could be a boon for a variety of research questions in the lab."
In the future, blocking CD47 might make it possible to generate large numbers of healthy cells for therapies, such as alternatives to conventional bone marrow transplantation and complex tissue and organ bioengineering, he added.
Citation: "Thrombospondin-1 Signaling through CD47 Inhibits Self-renewal by Regulating c-Myc and Other Stem Cell Transcription Factors"; Sukhbir Kaur et al.; Scientific Reports, 2013; 3 DOI: 10.1038/srep01673
Contact: David D. Roberts, email@example.com
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|Title Annotation:||Advanced Stem Cell Technology|
|Publication:||Stem Cell Lab World|
|Date:||May 6, 2013|
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