Stem cell transplantation into the central nervous system and the control of differentiation

Recent advances in stem cell biology, including methods of cell amplificati on and control of differentiation in vitro, provide us with new and powerfu l tools with which to explore the cellular, molecular, and genetic factors affecting cell survival, proliferation, differentiation, and differentiatio n potential. Mitigating this vein of enthusiasm are the results of stem cel l transplantation studies, which highlight our inability to control the fat e of stem cell populations following transplantation to the central nervous system (CNS), Differentiation of transplanted cells is strongly influenced by the environmental signals and cellular deficiencies operating at the si te of implantation, over which we can exert little or no control. Where ste m cell transplantation-mediated repair of the injured CNS has been demonstr ated most successfully, the transplant environments have invariably been si mplistic, and transplantation into the complex and reactive environment of a CNS injury site generally results in migration from the site of implantat ion followed by glial cell differentiation, Together, these findings sugges t that the most significant advances for the stem cell transplantation fiel d will come from research strategies that include predifferentiation of ste m cells prior to transplant and studies that further our understanding of t he factors affecting stem cell differentiation in the complex environment o f the CNS in vivo. (C) 2001 Wiley-Liss, Inc.