KLF7-transfected Schwann cell graft transplantation promotes sciatic nerve regeneration

Abstract

Abstract: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 AAV2-KLF7 in vitro. Mice was 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 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.

AAV-KLF7 Promotes Descending Propriospinal Neuron Axonal Plasticity after Spinal Cord Injury

“…Instead, many investigators have looked toward regulators of gene networks such as transcription factors of various regeneration-associated pathways. Here, we expanded upon previous reports of improved axonal regeneration and functional recovery attributed to the regulatory factor KLF7 established in the injured CST [ 10 , 12 , 36 ]. The goal of this study was to determine whether KLF7 treatment could be a novel strategy for DPSN axonal plasticity and functional repair after SCI.…”

Schwann Cells Enhance Penetration of Regenerated Axons into Three-Dimensional Microchannels

“…SCs also migrate into the CNS and remyelinate axons SCI [19,20]. Since SCs secrete multiple growth factors, their inclusion show promise in therapeutic strategies for spinal cord repair [21][22][23][24]. In light of these benefits of SCs [25][26][27], we propose that SCs coupled with 3D channel scaffolds could aid axon regeneration in SCI.…”

Combination of BMSCs‐laden acellular nerve xenografts transplantation and G‐CSF administration promotes sciatic nerve regeneration

“…It was further supported by SEM observation that oval BMSCs adhered and grew on the vessel wall of basilar membrane and presented uniform distribution. Although very few research argued against persistent survival of the seed cells after BMSCs laden‐ANX grafting in vivo (Hou et al, ), our previous studies found that labeled Schwann cells or BMSCs remained detectable and secreted neurotrophic factors in acellular nerve allografts or ANX at 4–8 weeks posttransplantation, irrespective of the species of the acellular nerve grafts (Jia et al, ; Wang et al, ). ANX thereby supplies the facilitating medium for the survival, adhesion, migration, and neurotrophic factors secretion of the seed cells.…”

“…Autologous nerve grafts are identified as the optimal nerve substitutes, nevertheless, the limited source of donor nerves and triggered denervation restrict the clinical application. Great progresses have been made in exploring natural and artificial nerve alternatives in decades (Du, Chen, Qing, Yang, & Jia, ; Li et al, ; Wang et al, ). Based on the chemical extraction, developed by Sondell, Lundborg, and Kanje (), the natural peripheral nerves were prepared into acellular nerve grafts with bioactivity for allogeneic and heterologous transplantation.…”