Human umbilical cord mesenchymal stem cells transplantation promotes cutaneous wound healing of severe burned rats.

Human umbilical cord mesenchymal stem cells transplantation promotes cutaneous wound healing of severe burned rats.
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人脐带间充质干细胞移植促进严重烧伤大鼠皮肤创面愈合

DOI:
10.1371/journal.pone.0088348
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发表时间:
2014
期刊:
影响因子:
3.7
通讯作者:
Du J
Du J
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Liu L;Yu Y;Hou Y;Chai J;Duan H;Chu W;Zhang H;Hu Q;Du J

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严重烧伤是一种常见的高度致命的创伤。早期促进创面愈合是严重烧伤治疗的关键,有报道称间充质干细胞(MSC)治疗有助于创面愈合。本研究旨在探讨人脐血间充质干细胞(Huc-MSCs)对严重烧伤大鼠创面愈合的影响及其可能机制。成年雄性Wistar大鼠随机分为假手术组、烧伤组和烧伤组。各组分别静脉注射GFP标记的Huc-MSCs或PBS。采用Image Pro Plus软件评价伤口闭合率。通过体内生物发光成像(BLI)示踪GFP标记的Huc-MSCs,用聚合酶链式反应(PCR)检测创面组织中人特异性DNA的表达。组织化学染色检测创面炎性细胞、中性粒细胞、巨噬细胞、毛细血管和I/III型胶原。用激光多普勒血流仪测定创面血流量。用双抗体夹心法检测创面促炎和抗炎因子、血管内皮生长因子、I/III型胶原的水平。我们发现,在Huc-MSC治疗组,伤口愈合明显加快。HUC-MSCs向创面迁移,显著降低创面炎症细胞数量和IL-1、IL-6、肿瘤坏死因子-α水平,升高IL-10、TsG-6水平。此外,Huc-MSC治疗组创面新生血管和血管内皮生长因子水平明显高于其他对照组。在移植后各时间点,Huc-MSC治疗组的I、III型胶原比例明显高于烧伤组。提示Huc-MSCs移植能有效促进严重烧伤大鼠创面愈合。为HUC-MSC在烧伤创面的进一步临床应用提供了理论依据。
Severe burns are a common and highly lethal trauma. The key step for severe burn therapy is to promote the wound healing as early as possible, and reports indicate that mesenchymal stem cell (MSC) therapy contributes to facilitate wound healing. In this study, we investigated effect of human umbilical cord MSCs (hUC-MSCs) could on wound healing in a rat model of severe burn and its potential mechanism. Adult male Wistar rats were randomly divided into sham, burn, and burn transplanted hUC-MSCs. GFP labeled hUC-MSCs or PBS was intravenous injected into respective groups. The rate of wound closure was evaluated by Image Pro Plus. GFP-labeled hUC-MSCs were tracked by in vivo bioluminescence imaging (BLI), and human-specific DNA expression in wounds was detected by PCR. Inflammatory cells, neutrophils, macrophages, capillaries and collagen types I/III in wounds were evaluated by histochemical staining. Wound blood flow was evaluated by laser Doppler blood flow meter. The levels of proinflammatory and anti-inflammatory factors, VEGF, collagen types I/III in wounds were analyzed using an ELISA. We found that wound healing was significantly accelerated in the hUC-MSC therapy group. The hUC-MSCs migrated into wound and remarkably decreased the quantity of infiltrated inflammatory cells and levels of IL-1, IL-6, TNF-α and increased levels of IL-10 and TSG-6 in wounds. Additionally, the neovascularization and levels of VEGF in wounds in the hUC-MSC therapy group were markedly higher than those in other control groups. The ratio of collagen types I and III in the hUC-MSC therapy group were markedly higher than that in the burn group at indicated time after transplantation. The study suggests that hUC-MSCs transplantation can effectively improve wound healing in severe burned rat model. Moreover, these data might provide the theoretical foundation for the further clinical application of hUC-MSC in burn areas.
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