Extramedullary chitosan channels promote survival of transplanted neural stem and progenitor cells and create a tissue bridge after complete spinal cord transection.
Transplantation of neural stem and progenitor cells (NSPCs) is a promising strategy for repair after spinal cord injury. However, the epicenter of the severely damaged spinal cord is a hostile environment that results in poor survival of the transplanted NSPCs. We examined implantation of extramedullary chitosan channels seeded with NSPCs derived from transgenic green fluorescent protein (GFP) rats after spinal cord transection (SCT). At 14 weeks, we assessed the survival, maturation, and functional results using NSPCs harvested from the brain (brain group) or spinal cord (SC group) and seeded into chitosan channels implanted between the cord stumps after complete SCT. Control SCT animals had empty chitosan channels or no channels implanted. Channels seeded with brain or spinal cord-derived NSPCs showed a tissue bridge, although the bridges were thicker in the brain group. Both cell types showed long-term survival, but the number of surviving cells in the brain group was approximately five times as great as in the SC group. In both the brain and SC groups at 14 weeks after transplantation, many host axons were present in the center of the bridge in association with the transplanted cells. At 14 weeks astrocytic and oligodendrocytic differentiation in the channels was 24.8% and 17.3%, respectively, in the brain group, and 31.8% and 9.7%, respectively, in the SC group. The channels caused minimal tissue reaction in the adjacent spinal cord. There was no improvement in locomotor function. Thus, implantation of chitosan channels seeded with NSPCs after SCT created a tissue bridge containing many surviving transplanted cells and host axons, although there was no functional improvement.
Nomura
Hiroshi
H
Toronto Western Research Institute, Toronto Western Hospital, Toronto, Ontario, Canada.
Zahir
Tasneem
T
Kim
Howard
H
Katayama
Yusuke
Y
Kulbatski
Iris
I
Morshead
Cindi M
CM
Shoichet
Molly S
MS
Tator
Charles H
CH
D000818:Animals; D030801:Animals, Genetically Modified; D002454:Cell Differentiation; D002470:Cell Survival; D048271:Chitosan; D005260:Female; D049452:Green Fluorescent Proteins / Q000235:genetics; D008297:Male; D046529:Microscopy, Electron, Transmission; D039902:Multipotent Stem Cells / Q000166:cytology* / Q000378:metabolism / Q000637:transplantation*; D009474:Neurons / Q000166:cytology* / Q000378:metabolism / Q000637:transplantation*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000235:genetics; D013119:Spinal Cord Injuries / Q000378:metabolism / Q000473:pathology / Q000601:surgery*; D033581:Stem Cell Transplantation / Q000379:methods; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds
D011994:Recombinant Proteins; D049452:Green Fluorescent Proteins; D048271:Chitosan