Comparison of pure and mixed populations of human fetal-derived neural progenitors transplanted into intact adult rat brain.
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.
Messina
Darin J
DJ
Program in Neuroscience, The Keck Center for Tissue Engineering, University of Utah, Salt Lake City, UT 84112, USA.
Alder
Lindsay
L
Tresco
Patrick A
PA
D000818:Animals; D016380:Brain Tissue Transplantation; D002454:Cell Differentiation; D016332:Fetal Tissue Transplantation; D006085:Graft Survival; D006801:Humans; D007150:Immunohistochemistry; D007381:Intermediate Filament Proteins / Q000378:metabolism; D009419:Nerve Tissue Proteins; D064231:Nestin; D039842:Neural Cell Adhesion Molecule L1 / Q000378:metabolism; D009457:Neuroglia / Q000166:cytology* / Q000637:transplantation; D009474:Neurons / Q000166:cytology* / Q000637:transplantation; D010641:Phenotype; D051381:Rats; D012794:Sialic Acids / Q000378:metabolism; D033581:Stem Cell Transplantation
D007381:Intermediate Filament Proteins; C577484:NES protein, human; D009419:Nerve Tissue Proteins; C577486:Nes protein, rat; D064231:Nestin; D039842:Neural Cell Adhesion Molecule L1; D012794:Sialic Acids; C103469:polysialyl neural cell adhesion molecule