Pluripotent stem cells engrafted into the normal or lesioned adult rat spinal cord are restricted to a glial lineage.
Proliferating populations of undifferentiated neural stem cells were isolated from the embryonic day 14 rat cerebral cortex or the adult rat subventricular zone. These cells were pluripotent through multiple passages, retaining the ability to differentiate in vitro into neurons, astrocytes, and oligodendrocytes. Two weeks to 2 months after engraftment of undifferentiated, BrdU-labeled stem cells into the normal adult spinal cord, large numbers of surviving cells were seen. The majority of the cells differentiated with astrocytic phenotype, although some oligodendrocytes and undifferentiated, nestin-positive cells were detected; NeuN-positive neurons were not seen. Labeled cells were also engrafted into the contused adult rat spinal cord (moderate NYU Impactor injury), either into the lesion cavity or into the white or gray matter both rostral and caudal to the injury epicenter. Up to 2 months postgrafting, the majority of cells either differentiated into GFAP-positive astrocytes or remained nestin positive. No BrdU-positive neurons or oligodendrocytes were observed. These results show robust survival of engrafted stem cells, but a differentiated phenotype restricted to glial lineages. We suggest that in vitro induction prior to transplantation will be necessary for these cells to differentiate into neurons or large numbers of oligodendrocytes.
Cao
Q L
QL
Department of Neurological Surgery, University of Louisville School of Medicine, Louisville, Kentucky 40202, USA.
Zhang
Y P
YP
Howard
R M
RM
Walters
W M
WM
Tsoulfas
P
P
Whittemore
S R
SR
D000818:Animals; D000943:Antigens, Differentiation / Q000096:biosynthesis; D016380:Brain Tissue Transplantation / Q000379:methods; D001973:Bromodeoxyuridine; D002454:Cell Differentiation; D019070:Cell Lineage; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000196:embryology / Q000637:transplantation; D005260:Female; D016332:Fetal Tissue Transplantation; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006085:Graft Survival; D007381:Intermediate Filament Proteins / Q000378:metabolism; D009419:Nerve Tissue Proteins; D064231:Nestin; D009457:Neuroglia / Q000166:cytology* / Q000378:metabolism; D010641:Phenotype; D051381:Rats; D011916:Rats, Inbred F344; D013116:Spinal Cord / Q000473:pathology / Q000601:surgery*; D013119:Spinal Cord Injuries / Q000378:metabolism / Q000473:pathology / Q000601:surgery*; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D014949:Wounds, Nonpenetrating
D000943:Antigens, Differentiation; D005904:Glial Fibrillary Acidic Protein; D007381:Intermediate Filament Proteins; D009419:Nerve Tissue Proteins; C577486:Nes protein, rat; D064231:Nestin; D001973:Bromodeoxyuridine