8/17/2011 PERMALINK
Breakthrough eliminates a major risk associated with using stem cells to reverse effects of aging and disease. Chad Tang and colleagues at the Institute of Stem Cell Biology and Regenerative Medicine at Stanford University School of Medicine have found a way to prevent the application of stem cell therapies from causing tumors. An important risk in the clinical application of human pluripotent stem cells (hPSCs), including human embryonic and induced pluripotent stem cells (hESCs and hiPSCs), is teratoma formation by residual undifferentiated cells. A teratoma is an encapsulated tumor with the wrong kind of tissues which may be quite different from surrounding tissues and may be highly disparate; teratomas have been reported to contain hair, teeth, bone and, very rarely, more complex organs such as eyes, hands, feet, or other limbs.
The scientists were able to raise a monoclonal antibody against hESCs, designated anti–stage-specific embryonic antigen (SSEA)-5, which binds a previously unidentified antigen highly and specifically expressed on hPSCs—the H type-1 glycan. Separation based on SSEA-5 expression through fluorescence-activated cell sorting (FACS) greatly reduced teratoma-formation potential of heterogeneously differentiated cultures. To ensure complete removal of teratoma-forming cells, the researchers identified additional pluripotency surface markers (PSMs) exhibiting a large dynamic expression range during differentiation: CD9, CD30, CD50, CD90 and CD200. Immunohistochemistry studies of human fetal tissues and bioinformatics analysis of a microarray database revealed that concurrent expression of these markers is both common and specific to hPSCs. Immunodepletion with antibodies against SSEA-5 and two additional PSMs completely removed teratoma-formation potential from incompletely differentiated hESC cultures.