KLF7-transfected Schwann cell graft transplantation promotes sciatic nerve regeneration.
Our former study demonstrated that Krüppel-like Factor 7 (KLF7) is a transcription factor that stimulates axonal regeneration after peripheral nerve injury. Currently, we used a gene therapy approach to overexpress KLF7 in Schwann cells (SCs) and assessed whether KLF7-transfected SCs graft could promote sciatic nerve regeneration. SCs were transfected by adeno-associated virus 2 (AAV2)-KLF7 in vitro. Mice were allografted by an acellular nerve (ANA) with either an injection of DMEM (ANA group), SCs (ANA+SCs group) or AAV2-KLF7-transfected SCs (ANA+KLF7-SCs group) to assess repair of a sciatic nerve gap. The results indicate that KLF7 overexpression promoted the proliferation of both transfected SCs and native SCs. The neurite length of the dorsal root ganglia (DRG) explants was enhanced. Several beneficial effects were detected in the ANA+KLF7-SCs group including an increase in the compound action potential amplitude, sciatic function index score, enhanced expression of PKH26-labeling transplant SCs, peripheral myelin protein 0, neurofilaments, S-100, and myelinated regeneration nerve. Additionally, HRP-labeled motoneurons in the spinal cord, CTB-labeled sensory neurons in the DRG, motor endplate density and the weight ratios of target muscles were increased by the treatment while thermal hyperalgesia was diminished. Finally, expression of KLF7, NGF, GAP43, TrkA and TrkB were enhanced in the grafted SCs, which may indicate that several signal pathways may be involved in conferring the beneficial effects from KLF7 overexpression. We concluded that KLF7-overexpressing SCs promoted axonal regeneration of the peripheral nerve and enhanced myelination, which collectively proved KLF-SCs as a novel therapeutic strategy for injured nerves.
Department of Anatomy, Mudanjiang College of Medicine, Mudanjiang 157011, China.
Ying
Y
Wang
Department of Anatomy, Mudanjiang College of Medicine, Mudanjiang 157011, China. Electronic address: yingwang770224@163.com.
Wen-Yuan
WY
Li
Department of Anatomy, Ningxia Medical University, Yinchuan 750004, China.
Hua
H
Jia
Department of Pharmacology, Mudanjiang College of Medicine, Mudanjiang 157011, China.
Feng-Guo
FG
Zhai
Hand & Foot Surgery and Reparative & Reconstructive Surgery Center, Orthopaedic Hospital of the Second Hospital of Jilin University, Changchun 130041, China.
Wen-Rui
WR
Qu
Department of Pathology, Mudanjiang College of Medicine, Mudanjiang 157011, China.
Yong-Xia
YX
Cheng
Department of Anatomy, Mudanjiang College of Medicine, Mudanjiang 157011, China.
Yan-Cui
YC
Liu
Spinal Cord and Brain Injury Research Group, Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN 46202, United States.
Ling-Xiao
LX
Deng
Hand & Foot Surgery and Reparative & Reconstructive Surgery Center, Orthopaedic Hospital of the Second Hospital of Jilin University, Changchun 130041, China.
Su-Fen
SF
Guo
Hand & Foot Surgery and Reparative & Reconstructive Surgery Center, Orthopaedic Hospital of the Second Hospital of Jilin University, Changchun 130041, China.
Zai-Shun
ZS
Jin
D064591:Allografts; D000818:Animals; D002470:Cell Survival / Q000502:physiology; D018920:Coculture Techniques; D000229:Dependovirus / Q000235:genetics; D005260:Female; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D009043:Motor Activity / Q000502:physiology; D009045:Motor Endplate / Q000378:metabolism / Q000473:pathology; D009416:Nerve Regeneration / Q000502:physiology*; D055495:Neurogenesis / Q000502:physiology; D000071446:Neuronal Outgrowth / Q000502:physiology; D059348:Peripheral Nerve Injuries / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D011897:Random Allocation; D012583:Schwann Cells / Q000378:metabolism* / Q000473:pathology / Q000637:transplantation*; D012584:Sciatic Nerve / Q000293:injuries* / Q000378:metabolism* / Q000473:pathology; D014162:Transfection
D051741:Kruppel-Like Transcription Factors; D049452:Green Fluorescent Proteins
KLF7; SCs; axonal regeneration; myelination; peripheral nerve injury