A drug target that stimulates development of healthy stem cells
Scientists have overcome a major impediment to the development of effective stem cell therapies by studying mice that lack CD47, a protein found on the surface of both healthy and cancer cells. Researchers at the National Cancer Institute discovered that cells obtained from the lungs of CD47-deficient mice, but not from ordinary mice that have the CD47 gene, multiplied in a culture dish and spontaneously converted into stem cells. By adding specific growth factors, these stem cells could then be directed to become cells of any tissue type. More tests in animals are needed, but if they pan out it appears that injecting a drug that blocks CD47 in humans could stimulate patients to make more of their own stem cells, which could be used for regeneration of injured tissues and organs. This strategy would also bypass the rejection problems associated with using donor stem cells for therapy. David D. Roberts, Ph.D., chief of the Biochemical Pathology Section in the Center for Cancer Research, NCI, headed the study that appeared online in Scientific Reports on April 17, 2013.
The use of engineered viruses to deliver four specific genes, known as Yamanaka factors, into normal cells to stimulate their conversion into stem cells is a promising approach for developing new medical treatments. However, practical application has been limited by the tendency of these stem cells to be rejected by the body and, most importantly, to cause cancer. Roberts and colleagues found that expression of Yamanaka factors could be stimulated in normal cells by simply decreasing CD47 expression. The resulting stem cells thrived in culture but did not form tumors when injected into mice. As part of this study, the researchers also found that c-Myc, one of the Yamanaka factors and a gene that is mutated in many cancers, is regulated by CD47 in healthy cells but not in cancer cells. This may be one reason that CD47-targeted drugs can selectively protect healthy tissues from adverse side effects of radiation therapy, while enhancing tumor shrinkage. Insights into the relationship between c-Myc and CD47 provided in this publication may take scientists another step toward improved treatments for patients with cancer.