Implantation of BM mesenchymal stem cells into injured spinal cord elicits de novo neurogenesis and functional recovery: evidence from a study in rhesus monkeys.
BACKGROUND
Transplantation of mesenchymal stem cells (MSC) in rodent models has proved to be an effective therapeutic approach for spinal cord injury (SCI). However, further studies in primate models are still needed before clinical application of MSC to patients.


METHODS
MSC were isolated from rhesus monkey BM and induced ex vivo to differentiate into neural lineage cells. Induced cells were labeled with Hoechst 33342 and injected into the injured sites of rhesus SCI models. Function of the injured spinal cord was assessed using Tarlov behavior assessment, sensory responses and electrophysiologic tests of cortical somatosensory-evoked potential (CSEP) and motor-evoked potential (MEP). In vivo differentiation of the implanted cells was demonstrated by the presence of neural cell markers in Hoechst 33342-labeled cells. The re-establishment of the axonal pathway was demonstrated using a true blue (TB) chloride retrograde tracing study.


RESULTS
Monkeys achieved Tarlov grades 2-3 and nearly normal sensory responses 3 months after cell transplantation. Both CSEP and MEP showed recovery features. The presence of the neural cell markers neurofilament (NF), neuro-specific enolase (NSE) and glial fibrillary acidic protein (GFAP) was observed in approximately 10% of Hoechst 33342-labeled cells. TB, originally injected at the caudal side of injured sites, was traceable in the rostral thoracic spinal cord, red nucleus and sensory motor cortex.


CONCLUSIONS
Our results suggest that the implantation of MSC-derived cells elicits de novo neurogenesis and functional recovery in a non-human primate SCI model and should harness the clinical application of BM MSC in SCI patients.
Deng
Y-B
YB
Department of Pathophysiology, Sun Yat-Sen University, Guangzhou 510089, China. albert@gzsums.edu.cn
Liu
X-G
XG
Liu
Z-G
ZG
Liu
X-L
XL
Liu
Y
Y
Zhou
G-Q
GQ
D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D001854:Bone Marrow Cells / Q000166:cytology; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000187:drug effects; D002469:Cell Separation; D004365:Drugs, Chinese Herbal / Q000494:pharmacology; D004594:Electrophysiology; D019054:Evoked Potentials, Motor / Q000502:physiology; D005073:Evoked Potentials, Somatosensory / Q000502:physiology; D015870:Gene Expression / Q000235:genetics; D005968:Glutamate Decarboxylase / Q000235:genetics; D007527:Isoenzymes / Q000235:genetics; D008253:Macaca mulatta; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000737:chemistry / Q000166:cytology / Q000378:metabolism; D009416:Nerve Regeneration; D010616:Phenanthrenes / Q000494:pharmacology; D020127:Recovery of Function; D013119:Spinal Cord Injuries / Q000503:physiopathology / Q000628:therapy*; D016896:Treatment Outcome
D015703:Antigens, CD; D004365:Drugs, Chinese Herbal; D007527:Isoenzymes; D010616:Phenanthrenes; C037886:cryptotanshinone; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1; C401141:glutamate decarboxylase 2