Transplantation of Schwann cells and/or olfactory ensheathing glia into the contused spinal cord: Survival, migration, axon association, and functional recovery.
Schwann cells (SCs) and olfactory ensheathing glia (OEG) have shown promise for spinal cord injury repair. We sought their in vivo identification following transplantation into the contused adult rat spinal cord at 1 week post-injury by: (i) DNA in situ hybridization (ISH) with a Y-chromosome specific probe to identify male transplants in female rats and (ii) lentiviral vector-mediated expression of EGFP. Survival, migration, and axon-glia association were quantified from 3 days to 9 weeks post-transplantation. At 3 weeks after transplantation into the lesion, a 60-90% loss of grafted cells was observed. OEG-only grafts survived very poorly within the lesion (<5%); injection outside the lesion led to a 60% survival rate, implying that the injury milieu was hostile to transplanted cells and or prevented their proliferation. At later times post-grafting, p75(+)/EGFP(-) cells in the lesion outnumbered EGFP(+) cells in all paradigms, evidence of significant host SC infiltration. SCs and OEG injected into the injury failed to migrate from the lesion. Injection of OEG outside of the injury resulted in their migration into the SC-injected injury site, not via normal-appearing host tissue but along the pia or via the central canal. In all paradigms, host axons were seen in association with or ensheathed by transplanted glia. Numerous myelinated axons were found within regions of grafted SCs but not OEG. The current study details the temporal survival, migration, axon association of SCs and OEG, and functional recovery after grafting into the contused spinal cord, research previously complicated due to a lack of quality, long-term markers for cell tracking in vivo.
Pearse
Damien D
DD
Department of Neurological Surgery, University of Miami Miller School of Medicine, Miami, FL, USA. DPearse@miamiproject.med.miami.edu
Sanchez
Andre R
AR
Pereira
Francisco C
FC
Andrade
Christian M
CM
Puzis
Raisa
R
Pressman
Yelena
Y
Golden
Kevin
K
Kitay
Brandon M
BM
Blits
Bas
B
Wood
Patrick M
PM
Bunge
Mary Bartlett
MB
D000818:Animals; D030801:Animals, Genetically Modified; D001369:Axons / Q000502:physiology / Q000648:ultrastructure; D016380:Brain Tissue Transplantation / Q000379:methods*; D002450:Cell Communication / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D005260:Female; D005819:Genetic Markers / Q000235:genetics; D005838:Genotype; D006085:Graft Survival / Q000502:physiology*; D049452:Green Fluorescent Proteins / Q000235:genetics; D008297:Male; D009434:Neural Pathways / Q000166:cytology / Q000502:physiology; D009830:Olfactory Bulb / Q000166:cytology / Q000637:transplantation*; D051381:Rats; D011916:Rats, Inbred F344; D020127:Recovery of Function / Q000502:physiology*; D012583:Schwann Cells / Q000637:transplantation*; D013119:Spinal Cord Injuries / Q000628:therapy*; D016896:Treatment Outcome; D014998:Y Chromosome / Q000235:genetics
D005819:Genetic Markers; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins