Bridging small-gap peripheral nerve defects using acellular nerve allograft implanted with autologous bone marrow stromal cells in primates.
This study evaluated the effects of the transplantation of a tissue-engineered nerve derived from an acellular allogenic nerve graft, combined with autologous bone marrow stromal cells (MSCs), into peripheral nerve defects. In a rhesus monkey model, nerve regeneration was evaluated across a 1-cm lesion in the radial nerve by using an acellular allogenic nerve injected with autologous MSCs. Simple acellular nerve allografts served as control. Eight weeks after surgery, immunofluorescence staining, histologic morphometrical analysis and electrophysiologic evaluation were performed. Fluorescence microscopy revealed that some MSCs were immunopositive to S-100 protein, indicating a Schwann cell (SC) phenotype. The group treated with cultured MSCs showed a statistically higher number of nerve fibers, with well-shaped remyelinated axons. The motor conduction velocities and the peak amplitudes of compound muscle action potentials (CMAP) for the group treated with MSCs were higher than those of the controls. This outcome indicated that MSCs are able to differentiate into Schwann-like cells in vivo and to promote nerve regeneration in primates. Furthermore, the acellular nerves injected with MSCs provided a favorable environment for the growth and myelination of regenerating axons when compared to acellular nerves alone.
Wang
Dong
D
Department of Orthopedic and Microsurgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, PR China.
Liu
Xiao-Lin
XL
Zhu
Jia-Kai
JK
Jiang
Li
L
Hu
Jun
J
Zhang
Yang
Y
Yang
Li-Min
LM
Wang
Hong-Gang
HG
Yi
Jian-Hua
JH
D000200:Action Potentials / Q000502:physiology; D000818:Animals; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D016026:Bone Marrow Transplantation / Q000379:methods*; D018929:Cell Culture Techniques / Q000379:methods; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D003470:Culture Media / Q000494:pharmacology; D004195:Disease Models, Animal; D005455:Fluorescent Antibody Technique; D020439:Growth Cones / Q000502:physiology / Q000648:ultrastructure; D008253:Macaca mulatta; D008297:Male; D046529:Microscopy, Electron, Transmission; D009416:Nerve Regeneration / Q000502:physiology*; D009431:Neural Conduction / Q000502:physiology; D059348:Peripheral Nerve Injuries; D010525:Peripheral Nerves / Q000502:physiology / Q000637:transplantation*; D011826:Radial Nerve / Q000502:physiology / Q000601:surgery / Q000648:ultrastructure; D009418:S100 Proteins / Q000032:analysis / Q000378:metabolism; D012583:Schwann Cells / Q000378:metabolism / Q000648:ultrastructure; D033581:Stem Cell Transplantation / Q000379:methods*; D017154:Stromal Cells / Q000502:physiology / Q000637:transplantation* / Q000648:ultrastructure; D014184:Transplantation, Homologous / Q000379:methods
D015415:Biomarkers; D003470:Culture Media; D009418:S100 Proteins