Human adult olfactory neural progenitors promote axotomized rubrospinal tract axonal reinnervation and locomotor recovery.
We investigated the effects of engrafted human adult olfactory neuroepithelial neurosphere forming cells (NSFCs) on regeneration and reinnervation of rubrospinal tract (RST) axons and locomotor recovery following partial cervical hemisection that completely ablated the RST. Weekly behavioral testing showed greater functional recovery of forelimb use during the 12 weeks after NSFCs engraftment than in the control rats. Anterograde tracing with biotinylated dextran amine (BDA) confirmed the presence of RST axons within the white matter 4-8 segments caudal to the grafts. Both immunofluorescence and immunoelectron microscopy revealed the BDA-labeled RST axonal terminals reestablished synaptic connections with motoneurons in the ventral horn of the distal cervical spinal cord. Further study of forelimb functional recovery in NSFCs-engrafted subgroups considered the effects of a second dorsolateral funiculotomy, irreversibly destroying the recovery, and the injection of muscimol, blocking RST neuronal activity reversibly. These results highlight the unique potential of human olfactory neuroepithelial-derived progenitors as an autologous cell source for spinal cord repair.
Xiao
Ming
M
Department of Human Anatomy, Histology and Embryology, Nanjing Medical University, Nanjing, 210029 China. mingx@njmu.edu.cn
Klueber
Kathleen M
KM
Zhou
JianPing
J
Guo
Zhanfang
Z
Lu
Chengliang
C
Wang
Heming
H
Roisen
Fred J
FJ
D000818:Animals; D019771:Axotomy; D001710:Biotin / Q000031:analogs & derivatives; D016380:Brain Tissue Transplantation / Q000379:methods*; D003911:Dextrans; D004525:Efferent Pathways / Q000293:injuries / Q000503:physiopathology / Q000601:surgery; D005260:Female; D005552:Forelimb / Q000294:innervation / Q000503:physiopathology; D006085:Graft Survival / Q000502:physiology; D006801:Humans; D016253:Microscopy, Immunoelectron; D009043:Motor Activity / Q000502:physiology; D009416:Nerve Regeneration / Q000502:physiology*; D009830:Olfactory Bulb / Q000166:cytology / Q000502:physiology / Q000637:transplantation; D010243:Paralysis / Q000209:etiology / Q000503:physiopathology / Q000628:therapy; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000502:physiology*; D012012:Red Nucleus / Q000166:cytology / Q000502:physiology; D013116:Spinal Cord / Q000503:physiopathology / Q000601:surgery*; D013119:Spinal Cord Injuries / Q000503:physiopathology / Q000628:therapy*; D033581:Stem Cell Transplantation / Q000379:methods*; D013234:Stem Cells / Q000166:cytology / Q000502:physiology; D014183:Transplantation, Heterologous; D016896:Treatment Outcome
D003911:Dextrans; C076397:biotinylated dextran amine; D001710:Biotin