Voluntary Exercise Positively Affects the Recovery of Long-Nerve Gap Injury Following Tube-Bridging with Human Skeletal Muscle-Derived Stem Cell Transplantation
by
Hiroya Seta 1,2, Daisuke Maki 1,3
, Akihito Kazuno 1,4, Ippei Yamato 1,5, Nobuyuki Nakajima 1,6, Shuichi Soeda 1, Yoshiyasu Uchiyama 1,7 and Tetsuro Tamaki 1,2,*
Hiroya Seta 1,2, Daisuke Maki 1,3, Akihito Kazuno 1,4, Ippei Yamato 1,5, Nobuyuki Nakajima 1,6, Shuichi Soeda 1, Yoshiyasu Uchiyama 1,7 and Tetsuro Tamaki 1,2,*
1
Muscle Physiology & Cell Biology Unit, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa 259-1193, Japan
2
Department of Human Structure and Function, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa 259-1193, Japan
3
Department of Otolaryngology, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa 259-1193, Japan
4
Department of Surgery, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa 259-1193, Japan
5
Department of Medical Education, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa 259-1193, Japan
6
Department of Urology, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa 259-1193, Japan
7
Department of Orthopedics, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa 259-1193, Japan
*
Author to whom correspondence should be addressed.
J. Clin. Med. 2018, 7(4), 67; https://doi.org/10.3390/jcm7040067
Received: 5 March 2018 / Revised: 22 March 2018 / Accepted: 26 March 2018 / Published: 2 April 2018
(This article belongs to the Special Issue Injury and Repair in the Nervous System)
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.
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Keywords:
motor nerve function; tetanic tension; sensory nerve function; p75; N200; myelin basic protein
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MDPI and ACS Style
Seta, H.; Maki, D.; Kazuno, A.; Yamato, I.; Nakajima, N.; Soeda, S.; Uchiyama, Y.; Tamaki, T. Voluntary Exercise Positively Affects the Recovery of Long-Nerve Gap Injury Following Tube-Bridging with Human Skeletal Muscle-Derived Stem Cell Transplantation. J. Clin. Med. 2018, 7, 67.
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