Molecular examination of bone marrow stromal cells and chondroitinase ABC‑assisted acellular nerve allograft for peripheral nerve regeneration

Wang,Ying; Jia,Hua; Li,Wen‑Yuan; Guan,Li‑Xin; Deng,Lingxiao; Liu,Yan‑Cui; Liu,Gui‑Bo

doi:10.3892/etm.2016.3585

Molecular examination of bone marrow stromal cells and chondroitinase ABC‑assisted acellular nerve allograft for peripheral nerve regeneration

Authors:
- Ying Wang
- Hua Jia
- Wen‑Yuan Li
- Li‑Xin Guan
- Lingxiao Deng
- Yan‑Cui Liu
- Gui‑Bo Liu
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Affiliations: Department of Anatomy, Mudanjiang College of Medicine, Mudanjiang, Heilongjiang 157011, P.R. China, Department of Anatomy, College of Basic Medical Sciences, Ningxia Medical University, Yinchuan, Ningxia Hui 750004, P.R. China, Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, IN 46202, USA
Published online on: August 10, 2016 https://doi.org/10.3892/etm.2016.3585
Pages: 1980-1992
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The present study aimed to evaluate the molecular mechanisms underlying combinatorial bone marrow stromal cell (BMSC) transplantation and chondroitinase ABC (Ch‑ABC) therapy in a model of acellular nerve allograft (ANA) repair of the sciatic nerve gap in rats. Sprague Dawley rats (n=24) were used as nerve donors and Wistar rats (n=48) were randomly divided into the following groups: Group I, Dulbecco's modified Eagle's medium (DMEM) control group (ANA treated with DMEM only); Group II, Ch‑ABC group (ANA treated with Ch‑ABC only); Group III, BMSC group (ANA seeded with BMSCs only); Group IV, Ch‑ABC + BMSCs group (Ch‑ABC treated ANA then seeded with BMSCs). After 8 weeks, the expression of nerve growth factor, brain‑derived neurotrophic factor and vascular endothelial growth factor in the regenerated tissues were detected by reverse transcription‑quantitative polymerase chain reaction and immunohistochemistry. Axonal regeneration, motor neuron protection and functional recovery were examined by immunohistochemistry, horseradish peroxidase retrograde neural tracing and electrophysiological and tibialis anterior muscle recovery analyses. It was observed that combination therapy enhances the growth response of the donor nerve locally as well as distally, at the level of the spinal cord motoneuron and the target muscle organ. This phenomenon is likely due to the propagation of retrograde and anterograde transport of growth signals sourced from the graft site. Collectively, growth improvement on the donor nerve, target muscle and motoneuron ultimately contribute to efficacious axonal regeneration and functional recovery. Thorough investigation of molecular peripheral nerve injury combinatorial strategies are required for the optimization of efficacious therapy and full functional recovery following ANA.

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