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纳米支架负载人牙髓间充质干细胞或其分泌物可促进创面愈合。

A nanoscaffold impregnated with human wharton's jelly stem cells or its secretions improves healing of wounds.

机构信息

Department of Obstetrics and Gynaecology, Yong Yoo Lin School of Medicine, National University Health System, National University of Singapore, Kent Ridge, Singapore, 119228, Singapore.

出版信息

J Cell Biochem. 2014 Apr;115(4):794-803. doi: 10.1002/jcb.24723.

Abstract

Wound healing is a major problem in diabetic patients and current methods of treatment have met with limited success. Since skin cell renewal is under the control of mesenchymal stem cells (MSCs) treatment of wounds has been attempted with the application of exogenous bone marrow MSCs (hBMMSCs). However, hBMMSCs have the limitations of painful harvest, low cell numbers and short-lived stemness properties unlike MSCs from the Wharton's jelly of human umbilical cords (hWJSCs). Since nanoscaffolds provide three dimensional architectural patterns that mimic in vivo stem cell niches and aloe vera has antibacterial properties we evaluated the use of an aloe vera-polycaprolactone (AV/PCL) nanoscaffold impregnated with green fluorescent protein (GFP)-labeled hWJSCs (GFP-hWJSCs + AV/PCL) or its conditioned medium (hWJSC-CM + AV/PCL) for healing of excisional and diabetic wounds. In skin fibroblast scratch-wound assays exposed to GFP-hWJSCs + AV/PCL or hWJSC-CM + AV/PCL, fibroblasts migrated significantly faster from edges of scratches into vacant areas together with increased secretion of collagen I and III, elastin, fibronectin, superoxide dismutase, and metalloproteinase-1 (MMP-1) compared to controls. After one application of GFP-hWJSCs + AV/PCL or hWJSC-CM + AV/PCL excisional and diabetic wounds in mice showed rapid wound closure, reepithelialization, and increased numbers of sebaceous glands and hair follicles compared to controls. The same wounds exposed to GFP-hWJSCs + AV/PCL or hWJSC-CM + AV/PCL also showed positive keratinocyte markers (cytokeratin, involucrin, filaggrin) and increased expression of ICAM-1, TIMP-1, and VEGF-A compared to controls. AV/PCL nanoscaffolds in combination with hWJSCs appear to have synergistic benefits for wound healing.

摘要

伤口愈合是糖尿病患者的一个主要问题,目前的治疗方法收效有限。由于皮肤细胞的更新受间充质干细胞(MSCs)的控制,因此已经尝试通过应用外源性骨髓间充质干细胞(hBMMSCs)来治疗伤口。然而,hBMMSCs 存在疼痛采集、细胞数量少和短暂的干细胞特性等局限性,与来自人脐带华通氏胶(hWJSCs)的 MSCs 不同。由于纳米支架提供了模仿体内干细胞龛的三维建筑模式,并且芦荟具有抗菌特性,因此我们评估了使用芦荟-聚己内酯(AV/PCL)纳米支架浸渍绿色荧光蛋白(GFP)标记的 hWJSCs(GFP-hWJSCs+AV/PCL)或其条件培养基(hWJSC-CM+AV/PCL)治疗切口和糖尿病伤口的效果。在暴露于 GFP-hWJSCs+AV/PCL 或 hWJSC-CM+AV/PCL 的皮肤成纤维细胞划痕伤口测定中,与对照组相比,成纤维细胞从划痕边缘更快地迁移到空缺区域,同时胶原蛋白 I 和 III、弹性蛋白、纤维连接蛋白、超氧化物歧化酶和金属蛋白酶-1(MMP-1)的分泌也增加。与对照组相比,在小鼠的一次 GFP-hWJSCs+AV/PCL 或 hWJSC-CM+AV/PCL 应用后,切口和糖尿病伤口迅速闭合、上皮再形成,并且皮脂腺和毛囊的数量增加。暴露于 GFP-hWJSCs+AV/PCL 或 hWJSC-CM+AV/PCL 的相同伤口也显示出阳性角质形成细胞标志物(细胞角蛋白、内披蛋白、丝聚合蛋白)和细胞间黏附分子-1(ICAM-1)、基质金属蛋白酶抑制剂-1(TIMP-1)和血管内皮生长因子-A(VEGF-A)的表达增加。与 hWJSCs 结合的 AV/PCL 纳米支架似乎对伤口愈合具有协同作用。

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