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人脐带间充质干细胞来源的外泌体通过促进 M2 巨噬细胞极化、血管生成和胶原沉积加速糖尿病创面愈合。

Exosomes Derived from Human Umbilical Cord Mesenchymal Stem Cells Accelerate Diabetic Wound Healing via Promoting M2 Macrophage Polarization, Angiogenesis, and Collagen Deposition.

机构信息

Wuxi School of Medicine, Jiangnan University, Wuxi 214122, China.

School of Life Sciences and Heath Engineering, Jiangnan University, Wuxi 214122, China.

出版信息

Int J Mol Sci. 2022 Sep 9;23(18):10421. doi: 10.3390/ijms231810421.


DOI:10.3390/ijms231810421
PMID:36142334
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9498995/
Abstract

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-α (TNF-α), 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-α 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.

摘要

一些学者提出,来源于人脐带间充质干细胞(hucMSCs-exo)的外泌体的临床应用可能代表了改善糖尿病创面愈合的一种新策略。然而,hucMSCs-exo 对创面愈合影响的作用机制仍知之甚少。本研究旨在确定 hucMSCs-exo 治疗糖尿病创面的机制。从人脐带间充质干细胞(hucMSCs)中分离 hucMSCs-exo,并皮下注射到糖尿病大鼠的全层创面中。进行创面愈合闭合率和组织学分析。通过免疫组织化学检测肿瘤坏死因子-α(TNF-α)、巨噬细胞甘露糖受体(MMR/CD206)、血小板内皮细胞黏附分子-1(PECAM-1/CD31)和血管内皮生长因子(VEGF)的水平。使用 Masson 三色染色法检测胶原沉积程度。从术后 0 天到 14 天对创面愈合进行大体评估,并在术后 3、7 和 14 天采集创面组织进行组织学检查。hucMSCs-exo 移植可促进糖尿病创面愈合。体外,hucMSCs-exo 促进人脐静脉内皮细胞(HUVECs)和 NIH-3T3 细胞的增殖。在体内,hucMSCs-exo 减少创面面积和炎症浸润,增加胶原纤维。此外,hucMSCs-exo 组的创面组织在第 14 天的 CD206、CD31 和 VEGF 表达水平高于对照组,TNF-α 水平低于对照组。我们的结果表明,hucMSCs-exo 通过诱导抗炎型巨噬细胞和促进血管生成及胶原沉积促进糖尿病创面修复。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c232/9498995/acae46fa0395/ijms-23-10421-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c232/9498995/a8b1a33595d0/ijms-23-10421-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c232/9498995/77c8ad5e0575/ijms-23-10421-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c232/9498995/c2d86b27e37a/ijms-23-10421-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c232/9498995/e4d4e2733033/ijms-23-10421-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c232/9498995/18efe858fa7d/ijms-23-10421-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c232/9498995/ac7291df62f1/ijms-23-10421-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c232/9498995/acae46fa0395/ijms-23-10421-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c232/9498995/a8b1a33595d0/ijms-23-10421-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c232/9498995/77c8ad5e0575/ijms-23-10421-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c232/9498995/c2d86b27e37a/ijms-23-10421-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c232/9498995/e4d4e2733033/ijms-23-10421-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c232/9498995/18efe858fa7d/ijms-23-10421-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c232/9498995/ac7291df62f1/ijms-23-10421-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c232/9498995/acae46fa0395/ijms-23-10421-g007.jpg

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本文引用的文献

[1]
Extracellular vesicles: Emerging frontiers in wound healing.

Med Res Rev. 2022-11

[2]
Mesenchymal stem cell-derived exosomes: A novel and potential remedy for cutaneous wound healing and regeneration.

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Skin Wound Healing: Normal Macrophage Function and Macrophage Dysfunction in Diabetic Wounds.

Molecules. 2021-8-13

[10]
Exosomes derived from human umbilical cord blood mesenchymal stem cells stimulate regenerative wound healing via transforming growth factor-β receptor inhibition.

Stem Cell Res Ther. 2021-8-3

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