ABSTRACT: We examined the influence of initial graft composition on the number, type, and distribution of human progenitor cells after transplantation into the anterior subventricular zone (SVZa) of normal adult rats. The grafted populations were derived from 19-week-old human cortical tissue grown under adherent conditions in the presence of fibroblast growth factor (FGF) and from a subpopulation of nestin-expressing cells, isolated using negative immunoselection methods, which exhibited properties of neural progenitors. Identical numbers of each were transplanted and the number and location of engrafted cells were compared 4 weeks later. We found a significantly greater number of presumptive neurons and astrocytes in animals that received mixed grafts compared to those enriched for progenitors. In addition, the number of human cells undergoing division was significantly greater in animals that received mixed grafts. The spatial distribution of grafted cells was not significantly different, suggesting that the patterns of cell migration were unaffected by transplant composition, whereas, a greater proportion of neurons was observed in the neurogenic areas of animals that received progenitor-enriched grafts. From a clinical perspective, our results suggest that the cellular composition of human fetal-derived transplants may be an important parameter that influences the number and pattern of differentiation of engrafted cells following transplantation in the mature CNS.
Experimental Neurology 01/2004; 184(2):816-29. · 4.70 Impact Factor