PMID- 37443763 OWN - NLM STAT- MEDLINE DCOM- 20230717 LR - 20240131 IS - 2073-4409 (Electronic) IS - 2073-4409 (Linking) VI - 12 IP - 13 DP - 2023 Jun 27 TI - Efficacy of Rectal Systemic Administration of Mesenchymal Stem Cells to Injury Sites via the CXCL12/CXCR4 Axis to Promote Regeneration in a Rabbit Skeletal Muscle Injury Model. LID - 10.3390/cells12131729 [doi] LID - 1729 AB - 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. FAU - Ichiseki, Toru AU - Ichiseki T AD - Department of Orthopaedic Surgery, Kanazawa Medical University, Daigaku 1-1, Uchinada-machi, Kahoku 920-0293, Japan. FAU - Shimasaki, Miyako AU - Shimasaki M AD - Department of Pathology 2, Kanazawa Medical University, Daigaku 1-1, Uchinada-machi, Kahoku 920-0293, Japan. FAU - Ueda, Shusuke AU - Ueda S AUID- ORCID: 0000-0003-3385-032X AD - Department of Orthopaedic Surgery, Kanazawa Medical University, Daigaku 1-1, Uchinada-machi, Kahoku 920-0293, Japan. FAU - Hirata, Hiroaki AU - Hirata H AD - Department of Orthopaedic Surgery, Kanazawa Medical University, Daigaku 1-1, Uchinada-machi, Kahoku 920-0293, Japan. FAU - Souma, Daisuke AU - Souma D AD - Department of Orthopaedic Surgery, Kanazawa Medical University, Daigaku 1-1, Uchinada-machi, Kahoku 920-0293, Japan. FAU - Kawahara, Norio AU - Kawahara N AD - Department of Orthopaedic Surgery, Kanazawa Medical University, Daigaku 1-1, Uchinada-machi, Kahoku 920-0293, Japan. FAU - Ueda, Yoshimichi AU - Ueda Y AD - Department of Pathology, Keiju Medical Center, 94, Tomioka-machi, Nanao 926-0816, Japan. LA - eng GR - 20K09513, 19K18510,18K07002,19K18511/The Ministry of Education, Culture, Sports, Science, and Technology of Japan/ PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20230627 PL - Switzerland TA - Cells JT - Cells JID - 101600052 RN - 0 (Chemokine CXCL12) RN - 0 (Ligands) RN - 0 (Peptides) SB - IM MH - Animals MH - Rabbits MH - *Chemokine CXCL12/metabolism MH - Ligands MH - Muscle, Skeletal/metabolism MH - Peptides/metabolism MH - *Mesenchymal Stem Cells/metabolism PMC - PMC10340610 OTO - NOTNLM OT - C-X-C chemokine ligand 12 (CXCL12)/C-X-C chemokine receptor-4 (CXCR4) axis OT - cardiotoxin (CTX) OT - mesenchymal stem cells (MSCs) OT - myosin heavy polypeptide 3 (Myh3) COIS- The authors declare no conflict of interest. EDAT- 2023/07/14 13:06 MHDA- 2023/07/17 06:42 PMCR- 2023/06/27 CRDT- 2023/07/14 01:02 PHST- 2023/03/20 00:00 [received] PHST- 2023/06/22 00:00 [revised] PHST- 2023/06/22 00:00 [accepted] PHST- 2023/07/17 06:42 [medline] PHST- 2023/07/14 13:06 [pubmed] PHST- 2023/07/14 01:02 [entrez] PHST- 2023/06/27 00:00 [pmc-release] AID - cells12131729 [pii] AID - cells-12-01729 [pii] AID - 10.3390/cells12131729 [doi] PST - epublish SO - Cells. 2023 Jun 27;12(13):1729. doi: 10.3390/cells12131729.