cells and tissues formed are, in fact, fully functional and normal. Olle Lindvall, who works with Parkinson’s disease patients, noted that in some experiments in which dopaminergic neurons generated in culture were grafted into the brain of an animal, it was not at all clear that the new neurons were fully functional. The relationship between stem cell type and environmental cues makes problematic the assumption that stem cells cultured in vitro can be expected to perform with predictable results when transplanted in vivo (Morrison, 2001). It might be possible someday to provide cues to reprogram one cell type into another and even to culture these cells in vitro, but evidence of the normal physiological and restorative function of adult stem cells is very limited today.

A fifth limitation relevant to immediate development of therapies based on adult stem cells is the inability to maintain these cells in culture for very long before they differentiate into their mature progeny. One can envision two therapeutic approaches to stem cells. In the first, stem cells themselves are implanted in a diseased or injured organ in the hope that they will give rise to the mature cells needed by that organ. In the second, the stem cells are stimulated to differentiate into the needed mature tissue outside the body, and that tissue is implanted in the organ. That adult stem cells are difficult to isolate, purify, and culture causes problems for either approach, although even the ability to culture stem cells for a limited time, including in the presence of other cells, could have therapeutic potential. An example is the use of autologous skin grafts for burn patients, in which healthy skin (which contains skin stem cells) is removed from the patient, cultured briefly outside the body, and grafted onto the patient’s injured tissue. The grafts are not able to regenerate hair follicles and sweat glands, but are otherwise able to function normally. However, with a few exceptions, the appropriate culture conditions to sustain most adult stem cells indefinitely have yet to be found.

Very few stem cells, strictly defined, have even been isolated from adult human organs, in part because they constitute only a tiny fraction of the cells present and are not likely to be very distinct from the partially differentiated cells they give rise to as they mature and differentiate. For



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