Synergistic effects of G-CSF and bone marrow stromal cells on nerve regeneration with acellular nerve xenografts.
Peripheral nerve defects result in severe denervation presenting sensory and motor functional incapacitation. Currently, a satisfactory therapeutic treatment promoting the repair of injured nerves is not available. As shown in our previous study, acellular nerve xenografts (ANX) implanted with bone marrow stromal cells (BMSCs) replaced allografts and promoted nerve regeneration. Additionally, granulocyte-colony stimulating factor (G-CSF) has been proven to mobilize supplemental cells and enhance vascularization in the niche. Thus, the study aimed to explore whether the combination of G-CSF and BMSC-laden ANX exhibited a synergistic effect. Adult Sprague-Dawley (SD) rats were randomly divided into five groups: ANX group, ANX combined with G-CSF group, BMSCs-laden ANX group, BMSCs-laden ANX combined with G-CSF group and autograft group. Electrophysiological parameters and weight ratios of tibialis anterior muscles were detected at 8 weeks post-transplantation. The morphology of the regenerated nerves was assayed, and growth-promoting factors present in the nerve grafts following G-CSF administration or BMSCs seeding were also investigated. Nerve regeneration and functional rehabilitation induced by the combination therapy were significantly advanced, and the rehabilitation efficacy was comparable with autografting. Moreover, the expression of Schwann cell markers, neurotrophic factors and neovessel markers in the nerve grafts was substantially increased. In conclusion, G-CSF administration and BMSCs transplantation synergistically promoted the regeneration of ANX-bridged nerves, which offers a superior strategy to replace autografts in repairing peripheral nerve injuries.
Department of Anatomy, College of Basic Medical Sciences, Ningxia Medical University, Yinchuan, 750004, China.
Hua
0000-0002-1529-5054
H
Jia
Department of Anatomy, Mudanjiang College of Medicine, Mudanjiang, 157011, China.
Ying
Y
Wang
The Second Orthopedics Division, Armed Police Corps Hospital in Ningxia, Yinchuan, 750004, China.
Tao
T
Wang
Department of Orthopedics, General Hospital of Ningxia Medical University, Yinchuan, 750004, China.
Yi
Y
Dong
Department of Anatomy, College of Basic Medical Sciences, Ningxia Medical University, Yinchuan, 750004, China.
Wei-Li
WL
Li
Department of Anatomy, College of Basic Medical Sciences, Ningxia Medical University, Yinchuan, 750004, China.
Jun-Ping
JP
Li
Key Laboratory of Fertility Preservation and Maintenance of Ministry of Education, Key Laboratory of Reproduction and Genetic of Ningxia Hui Autonomous Region, and Department of Anatomy, Histology and Embryology, Ningxia Medical University, Yinchuan, 750004, China.
Wen-Zhi
WZ
Ma
Department of Anatomy, College of Basic Medical Sciences, China Medical University, Shenyang, 110001, China.
Xiao-Jie
XJ
Tong
Department of Anatomy, College of Basic Medical Sciences, Ningxia Medical University, Yinchuan, 750004, China.
Zhong-Yi
ZY
He
D000818:Animals; D002478:Cells, Cultured; D003131:Combined Modality Therapy; D004195:Disease Models, Animal; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage*; D045164:Mesenchymal Stem Cell Transplantation; D018482:Muscle, Skeletal / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D009186:Myelin Sheath / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D009416:Nerve Regeneration / Q000187:drug effects / Q000502:physiology; D000066530:Neurological Rehabilitation; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D009929:Organ Size; D059348:Peripheral Nerve Injuries / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D014182:Transplantation, Autologous; D014183:Transplantation, Heterologous; D014459:Ulnar Nerve / Q000637:transplantation*
D018696:Neuroprotective Agents; D012333:RNA, Messenger; D016179:Granulocyte Colony-Stimulating Factor
acellular nerve xenograft; bone marrow stromal cells; granulocyte-colony stimulating factor; peripheral nerve regeneration; transplantation