Viability-dependent promoting action of adult neural precursors in spinal cord injury.
The aim of the study was the assessment of the effects of adult neural stem cell (NSC) transplantation in a mouse model of spinal cord injury (SCI). The contusion injury was performed by means of the Infinite Horizon Device to allow the generation of reproducible traumatic lesion to the cord. We administered green fluorescent-labeled (GFP-)NSCs either by intravenous (i.v.) injection or by direct transplantation into the spinal cord (intraspinal route). We report that NSCs significantly improved recovery of hind limb function and greatly attenuated secondary degeneration. The i.v. route of NSC administration yielded better recovery than the intraspinal route of administration. About 2% of total i.v.-administered NSCs homed to the spinal cord injury site, and survived almost undifferentiated; thus the positive effect of NSC treatment cannot be ascribed to damaged tissue substitution. The NSCs homing to the injury site triggered, within 48 h, a large increase of the expression of neurotrophic factors and chemokines. One wk after transplantation, exogenous GFP-NSCs still retained their proliferation potential and produced neurospheres when recovered from the lesion site and cultured in vitro. At a later time, GFP-NSC were phagocytated by macrophages. We suggest that the process of triggering the recovery of function might be strongly related to the viability of GFP-NSC, still capable ex vivo of producing neurospheres, and their ability to modify the lesion environment in a positive fashion.
Bottai
Daniele
D
Department of Medicine, Surgery, and Dentistry, Faculty of Medicine, University of Milan, Milan, Italy.
Madaschi
Laura
L
Di Giulio
Anna M
AM
Gorio
Alfredo
A
D000818:Animals; D002454:Cell Differentiation; D002470:Cell Survival; D002478:Cells, Cultured; D004195:Disease Models, Animal; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D009043:Motor Activity; D009474:Neurons / Q000166:cytology / Q000637:transplantation*; D020127:Recovery of Function; D013116:Spinal Cord / Q000502:physiology / Q000601:surgery* / Q000637:transplantation; D013119:Spinal Cord Injuries / Q000601:surgery*; D033581:Stem Cell Transplantation / Q000379:methods*; D013234:Stem Cells / Q000166:cytology* / Q000502:physiology
D049452:Green Fluorescent Proteins