PMID- 36142334 OWN - NLM STAT- MEDLINE DCOM- 20220926 LR - 20220928 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 23 IP - 18 DP - 2022 Sep 9 TI - Exosomes Derived from Human Umbilical Cord Mesenchymal Stem Cells Accelerate Diabetic Wound Healing via Promoting M2 Macrophage Polarization, Angiogenesis, and Collagen Deposition. LID - 10.3390/ijms231810421 [doi] LID - 10421 AB - Some scholars have suggested that the clinical application of exosomes derived from human umbilical cord mesenchymal stem cells (hucMSCs-exo) might represent a novel strategy to improve diabetic wound healing. However, the mechanisms underlying the effects of hucMSCs-exo on wound healing remain poorly understood. This study aimed to identify the mechanism of hucMSCs-exo in treating diabetic wounds. HucMSCs-exo were isolated from human umbilical cord mesenchymal stem cells (hucMSCs) and subcutaneously injected into full-thickness wounds in diabetic rats. Wound healing closure rates and histological analysis were performed. The levels of tumor necrosis factor-alpha (TNF-alpha), macrophage mannose receptor (MMR/CD206), platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31), and vascular endothelial growth factor (VEGF) were detected by immunohistochemistry. The degree of collagen deposition was examined using Masson's trichrome staining. Gross evaluation of wound healing was carried out from day 0 to 14 post-surgery, and the wound site was harvested for histology on days 3, 7, and 14 post-wounding. HucMSCs-exo transplantation increased diabetic wound healing. In vitro, hucMSCs-exo promoted the proliferation of human umbilical vein endothelial cells (HUVECs) and NIH-3T3 cells. In vivo, hucMSCs-exo reduced wound area and inflammatory infiltration and increased collagen fibers. In addition, wound tissues in the hucMSCs-exo group had higher CD206, CD31, and VEGF expressions and lower TNF-alpha levels than those in the control group on day 14. Our results demonstrated that hucMSCs-exo facilitated diabetic wound repair by inducing anti-inflammatory macrophages and promoting angiogenesis and collagen deposition. FAU - Teng, Liping AU - Teng L AD - Wuxi School of Medicine, Jiangnan University, Wuxi 214122, China. FAU - Maqsood, Maria AU - Maqsood M AD - School of Life Sciences and Heath Engineering, Jiangnan University, Wuxi 214122, China. FAU - Zhu, Min AU - Zhu M AD - Wuxi School of Medicine, Jiangnan University, Wuxi 214122, China. FAU - Zhou, Yuting AU - Zhou Y AD - School of Life Sciences and Heath Engineering, Jiangnan University, Wuxi 214122, China. FAU - Kang, Mingzhu AU - Kang M AD - School of Life Sciences and Heath Engineering, Jiangnan University, Wuxi 214122, China. FAU - Zhou, Juan AU - Zhou J AUID- ORCID: 0000-0001-9770-7229 AD - School of Life Sciences and Heath Engineering, Jiangnan University, Wuxi 214122, China. FAU - Chen, Jinghua AU - Chen J AD - School of Life Sciences and Heath Engineering, Jiangnan University, Wuxi 214122, China. LA - eng PT - Journal Article DEP - 20220909 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (Platelet Endothelial Cell Adhesion Molecule-1) RN - 0 (Tumor Necrosis Factor-alpha) RN - 0 (Vascular Endothelial Growth Factor A) RN - 9007-34-5 (Collagen) SB - IM MH - Animals MH - Collagen/metabolism MH - *Diabetes Mellitus, Experimental/metabolism/therapy MH - *Exosomes/metabolism MH - Human Umbilical Vein Endothelial Cells/metabolism MH - Humans MH - Macrophages/metabolism MH - *Mesenchymal Stem Cells/metabolism MH - Mice MH - Neovascularization, Pathologic/metabolism MH - Platelet Endothelial Cell Adhesion Molecule-1/metabolism MH - Rats MH - Tumor Necrosis Factor-alpha/metabolism MH - Umbilical Cord MH - Vascular Endothelial Growth Factor A/metabolism MH - Wound Healing PMC - PMC9498995 OTO - NOTNLM OT - diabetes OT - exosomes OT - human-umbilical-cord-derived mesenchymal stem cells OT - macrophage polarization OT - wound healing COIS- The authors declare no conflict of interest. EDAT- 2022/09/24 06:00 MHDA- 2022/09/28 06:00 PMCR- 2022/09/09 CRDT- 2022/09/23 01:23 PHST- 2022/07/26 00:00 [received] PHST- 2022/08/05 00:00 [revised] PHST- 2022/08/07 00:00 [accepted] PHST- 2022/09/23 01:23 [entrez] PHST- 2022/09/24 06:00 [pubmed] PHST- 2022/09/28 06:00 [medline] PHST- 2022/09/09 00:00 [pmc-release] AID - ijms231810421 [pii] AID - ijms-23-10421 [pii] AID - 10.3390/ijms231810421 [doi] PST - epublish SO - Int J Mol Sci. 2022 Sep 9;23(18):10421. doi: 10.3390/ijms231810421.