Skeletal Muscle-Derived Stem Cell Transplantation Accelerates the Recovery of Peripheral Nerve Gap Injury under 50% and 100% Allogeneic Compatibility with the Swine Leucocyte Antigen

Author:

Tamaki Tetsuro12ORCID,Natsume Toshiharu12,Katoh Akira12ORCID,Shigenari Atsuko3,Shiina Takashi3,Nakajima Nobuyuki14ORCID,Saito Kosuke15,Fukuzawa Tsuyoshi16,Otake Masayoshi7,Enya Satoko7,Kangawa Akihisa7ORCID,Imai Takeshi18,Tamaki Miyu18,Uchiyama Yoshiyasu18

Affiliation:

1. Muscle Physiology and Cell Biology Unit, Tokai University School of Medicine, 143 Shimokasuya, Isehara 259-1193, Kanagawa, Japan

2. Department of Physiology, Tokai University School of Medicine, 143 Shimokasuya, Isehara 259-1193, Japan

3. Department of Molecular Life Science, Tokai University School of Medicine, 143 Shimokasuya, Isehara 259-1193, Japan

4. Department of Urology, Tokai University School of Medicine, 143 Shimokasuya, Isehara 259-1193, Japan

5. Department of Otolaryngology, Tokai University School of Medicine, 143 Shimokasuya, Isehara 259-1193, Japan

6. Department of Radiation Oncology, Tokai University School of Medicine, 143 Shimokasuya, Isehara 259-1193, Japan

7. Swine and Poultry Research Center, Shizuoka Prefectural Research Institute of Animal Industry, Kikugawa 439-0037, Shizuoka, Japan

8. Department of Orthopedic Surgery, Tokai University School of Medicine, 143 Shimokasuya, Isehara 259-1193, Japan

Abstract

Pig skeletal muscle-derived stem cells (SK-MSCs) were transplanted onto the common peroneal nerve with a collagen tube as a preclinical large animal experiment designed to address long nerve gaps. In terms of therapeutic usefulness, a human family case was simulated by adjusting the major histocompatibility complex to 50% and 100% correspondences. Swine leukocyte antigen (SLA) class I haplotypes were analyzed and clarified, as well as cell transplantation. Skeletal muscle-derived CD34+/45− (Sk-34) cells were injected into bridged tubes in two groups (50% and 100%) and with non-cell groups. Therapeutic effects were evaluated using sedentary/general behavior-based functional recovery score, muscle atrophy ratio, and immunohistochemistry. The results indicated that a two-Sk-34-cell-transplantation group showed clearly and significantly favorable functional recovery compared to a non-cell bridging-only group. Supporting functional recovery, the morphological reconstitution of the axons, endoneurium, and perineurium was predominantly evident in the transplanted groups. Thus, Sk-34 cell transplantation is effective for the regeneration of peripheral nerve gap injury. Additionally, 50% and 100% SLA correspondences were therapeutically similar and not problematic, and no adverse reaction was found in the 50% group. Therefore, the immunological response to Sk-MSCs is considered relatively low. The possibility of the Sk-MSC transplantation therapy may extend to the family members beyond the autologous transplantation.

Funder

Grant-in-Aid for Young Scientists (B) by the Ministry of Education, Culture, Sports, Science, and Technology

Publisher

MDPI AG

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