The Adult Neural Stem Cell Niche: Lessons for Future Neural Cell Replacement Strategies

Transplantation of neural stem cells (NSCs) and the mobilization of endogenous neural precursors in the adult brain have been proposed as therapies for a wide range of central nervous system disorders, including neurodegenerative disease (eg, Parkinson's disease), demyelinating disorders (eg, multiple sclerosis), stroke, and trauma. Although there is great hope for the success of such therapies, the clinical development of NSC-based therapies is still in its infancy. A greater understanding of how to control the proliferation, migration, differentiation, and survival of NSCs and their progeny is critical for the development of cell replacement therapies. NSCs are partially regulated by the specialized microenvironment--or "niche"--in which these cells reside. The adult rodent brain retains NSCs in two separate niches that continually generate new neurons: the subventricular zone (SVZ) of the lateral ventricle and the dentate gyrus subgranular zone (SGZ) of the hippocampus. Similar niches may be found in the human brain. In tis article, the authors briefly review their current understanding of the SVZ and SGZ niches. Lessons learned from these niches may allow one to manipulate NSCs better in culture for therapeutic transplantation and possibly even to mobilize endogenous precursors to repair diseased or injured brain.