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

Recent advances in stem cell biology, including methods of cell amplification and control of differentiation in vitro, provide us with new and powerful tools with which to explore the cellular, molecular, and genetic factors affecting cell survival, proliferation, differentiation, and differentiation potential. Mitigating this vein of enthusiasm are the results of stem cell transplantation studies, which highlight our inability to control the fate 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 site of implantation, over which we can exert little or no control. Where stem cell transplantation-mediated repair of the injured CNS has been demonstrated most successfully, the transplant environments have invariably been simplistic, and transplantation into the complex and reactive environment of a CNS injury site generally results in migration from the site of implantation followed by glial cell differentiation. Together, these findings suggest that the most significant advances for the stem cell transplantation field will come from research strategies that include predifferentiation of stem cells prior to transplant and studies that further our understanding of the factors affecting stem cell differentiation in the complex environment of the CNS in vivo.