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Stem Cells and the Future of Regenerative Medicine
example, at the workshop, Fred Gage discussed his work with cadavers and brain biopsy material, wherein he found not stem cells, but rather what might be more mature types of neural cell precursors (Palmer et al., 2001). Those cells would differentiate into various neural tissues but would then stop dividing. Unlike stem cells, precursors and other subsequent intermediates generally undergo limited self-renewal in vivo and are committed to a pathway of differentiation into a specific tissue type. Researchers are, however, beginning to understand how a stem cell gives rise to precursor cells and, in at least one case, have used this information to manipulate that process. Using biochemical signals found in the cellular environment, rodent precursor cells in vitro were caused to revert into more primitive, multipotent stem cells (Kondo and Raff, 2000). The ability to “reprogram” a cell may be exploited someday to therapeutic ends; however, the reversal of the normal pathway of differentiation may have biological consequences not yet detected. Rigorous experimentation will be needed to evaluate the implications of this basic research finding for regenerative medicine.
Finally, the implications of what is known about human adult stem cells are often overlooked amid reports of successes with experiments in rodents that simulate heart attack, retinal disease, and diabetes. Confirmed reports of truly multipotent human adult stem cells are scarce. For its recently released report on stem cells, the National Institutes of Health could find few published accounts of the isolation of multipotent adult stem cells from human tissues (NIH, 2001). The much-publicized recent report of stem cells from human fat that produced cartilage, bone, and muscle (Zuk et al., 2001), for example, did not conclusively establish that the cells capable of performing this feat were fat cells. The authors of the paper conceded that the observation might have been due to the presence of another cell type, such as an HSC that had circulated out of blood and into fat. Without conclusive identification, the existence of a multipotent fat cell remains unconfirmed.
That there is little evidence of a wide array of human adult stem cells that can differentiate into multiple tissue types does not mean that they will not eventually be found, nor should it be interpreted to mean that