Department of Orthopaedic Surgery, Kanazawa Medical University, Daigaku 1-1, Uchinada-machi, Kahoku 920-0293, Japan.
Department of Pathology 2, Kanazawa Medical University, Daigaku 1-1, Uchinada-machi, Kahoku 920-0293, Japan.
Cells. 2023 Jun 27;12(13):1729. doi: 10.3390/cells12131729.
Mesenchymal stem cells (MSCs) have been transplanted directly into lesions or injected intravenously. The administration of MSCs using these delivery methods requires specialized knowledge, techniques, and facilities. Here, we describe intrarectal systemic administration of MSCs, a simple, non-invasive route for homing to the injury sites to promote the regeneration of skeletal muscle injuries. Using a cardiotoxin (CTX)-induced rabbit skeletal muscle injury model, homing to the site of muscle injury was confirmed by intrarectal administration of MSCs; the time required for homing after intrarectal administration was approximately 5 days. In addition, the C-X-C chemokine ligand 12 (CXCL12)/C-X-C chemokine receptor-4 (CXCR4) axis was found to be involved in the homing process. Histopathological examinations showed that skeletal muscle regeneration was promoted in the MSCs-administered group compared to the CTX-only group. Myosin heavy polypeptide 3 (Myh3) expression, an indicator of early muscle regeneration, was detected earlier in the intrarectal MSCs group compared to the CTX-only group. These findings indicate that intrarectal administration of MSCs is effective in homing to the injured area, where they promote injury repair. Since intrarectal administration is a simple and non-invasive delivery route, these findings may be valuable in future research on stem cell therapy.
间充质干细胞（MSCs）已被直接移植到病变部位或静脉内注射。使用这些输送方法进行 MSCs 的给药需要专门的知识、技术和设施。在这里，我们描述了 MSCs 的直肠内全身给药，这是一种简单、非侵入性的途径，可以归巢到损伤部位，促进骨骼肌损伤的再生。使用心脏毒素（CTX）诱导的兔骨骼肌损伤模型，通过直肠内给予 MSCs 证实了归巢到肌肉损伤部位；直肠内给药后归巢所需的时间约为 5 天。此外，发现 C-X-C 趋化因子配体 12（CXCL12）/C-X-C 趋化因子受体 4（CXCR4）轴参与了归巢过程。组织病理学检查显示，与 CTX 组相比，给予 MSCs 的组促进了骨骼肌再生。肌球蛋白重链 3（Myh3）表达是早期肌肉再生的指标，在直肠内给予 MSCs 的组中比 CTX 组更早检测到。这些发现表明，直肠内给予 MSCs 可有效归巢到损伤区域，从而促进损伤修复。由于直肠内给药是一种简单且非侵入性的输送途径，这些发现可能对未来的干细胞治疗研究具有重要价值。
