Voluntary Exercise Positively Affects the Recovery of Long-Nerve Gap Injury Following Tube-Bridging with Human Skeletal Muscle-Derived Stem Cell Transplantation.

Hiroya Seta,Ippei Yamato,Akihito Kazuno,Yoshiyasu Uchiyama,Nobuyuki Nakajima,Shuichi Soeda,Tetsuro Tamaki,Daisuke Maki

doi:10.3390/jcm7040067

Hiroya Seta, Ippei Yamato + Show 6 more

Open Access

https://doi.org/10.3390/jcm7040067

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Journal: Journal of Clinical Medicine	Publication Date: Apr 2, 2018
Citations: 9	License type: CC BY 4.0

Affiliation: Tokai University

Abstract

The therapeutic effects of voluntary exercise on the recovery of long-gap nerve injury following the bridging of an acellular conduit filled with human skeletal muscle-derived stem cells (Sk-SCs) have been described. Human Sk-SCs were sorted as CD34+/45− (Sk-34) cells, then cultured/expanded under optimal conditions for 2 weeks. Surgery to generate a long-gap sciatic nerve injury was performed in athymic nude mice, after which the mice were divided into exercise (E) and non-exercise (NE) groups. The mice were housed in standard individual cages, and voluntary exercise wheels were introduced to the cages of the E group one week after surgery. After 8 weeks, the human Sk-34 cells were actively engrafted, and showed differentiation into Schwann cells and perineurial cells, in both groups. The recovery in the number of axons and myelin in the conduit and downstream tibial nerve branches, and the lower hindlimb muscle mass and their tension output, was consistently higher by 15–25% in the E group. Moreover, a significantly higher innervation ratio of muscle spindles, reduced pathological muscle fiber area, and acceleration of blood vessel formation in the conduit were each observed in the E group. These results showed that the combined therapy of tube-bridging, Sk-34 cell transplantation, and voluntary exercise is a potentially practical approach for recovery following long-gap nerve injury.

Highlights

Serious losses in the vital functions of the somatic nervous system are induced by long-gap peripheral nerve transection injuries caused by mechanical trauma, such as penetration, crush, traction or laceration [1,2], and typically result in poor functional recovery [3,4].various methods, such as bridging the nerve gap with a tube of some kind, combined with stem cell transplantation, have been attempted to improve recovery, as alternatives to the current surgical standard, nerve autograft therapy
Our results clearly indicate the positive effects of post-nerve injury exercise
Axon and myelin recovery was evaluated at the proximal site (Portion 1) and distal site (Portion 3)

Summary

Introduction

Serious losses in the vital functions of the somatic (motor and sensory) nervous system are induced by long-gap peripheral nerve transection injuries caused by mechanical trauma, such as penetration, crush, traction or laceration [1,2], and typically result in poor functional recovery [3,4]. Various methods, such as bridging the nerve gap with a tube of some kind, combined with stem cell transplantation, have been attempted to improve recovery, as alternatives to the current surgical standard, nerve autograft therapy. Treadmill exercise, performed during the first two weeks after peripheral nerve transection, was shown to enhance axon regeneration of the mouse common fibular nerves [7]

Results

Discussion

Conclusion