中国组织工程研究

中国组织工程研究 ›› 2024, Vol. 28 ›› Issue (13): 2047-2053.doi: 10.12307/2024.136

• 胚胎干细胞 embryonic stem cells • 上一篇    下一篇

胎盘间充质干细胞促进大鼠急性皮肤创面修复

董鸿斐1，2，黄  茜1，李先慧1，张彦标1，王旭阳3，4，王  冰3，4，孙红玉2，3，4   

  1. 西部战区总医院，1烧伤整形科，3基础实验室，四川省成都市   610083；2西南医科大学临床医学院，四川省泸州市   646000；4胰腺损伤与修复四川省重点实验室，四川省成都市   610083
  • 收稿日期:2023-02-14 接受日期:2023-04-17 出版日期:2024-05-08 发布日期:2023-08-28
  • 通讯作者: 孙红玉，博士，教授，西南医科大学临床医学院，四川省泸州市 646000；西部战区总医院基础实验室，四川省成都市 610083；胰腺损伤与修复四川省重点实验室，四川省成都市 610083
  • 作者简介:董鸿斐，男，1989年生，甘肃省天水市人，汉族，2021年西南医科大学毕业，硕士，主治医师，主要从事干细胞及干细胞外泌体联合组织工程支架在创面修复中的应用与机制研究。
  • 基金资助:
    国家自然科学基金面上项目(81772001)，项目负责人：孙红玉；腹部创伤分级救治及器官功能修复系列研究(2019LH04)，项目负责人：孙红玉；西部战区总医院院管课题孵化项目(2021-XZYG-C36)，项目负责人：黄茜

Placenta-derived mesenchymal stem cells in promoting acute skin wound healing in rats

Dong Hongfei1, 2, Huang Xi1, Li Xianhui1, Zhang Yanbiao1, Wang Xuyang3, 4, Wang Bing3, 4, Sun Hongyu2, 3, 4   

  1. 1Department of Burns and Plastic Surgery, General Hospital of Western Theater Command, Chengdu 610083, Sichuan Province, China; 2Department of School of Clinical Medicine, Southwest Medical University, Luzhou 646000, Sichuan Province, China; 3Department of Basic Center Laboratory, General Hospital of Western Theater Command, Chengdu 610083, Sichuan Province, China; 4Sichuan Provincial Key Laboratory of Pancreatic Injury and Repair, Chengdu 610083, Sichuan Province, China
  • Received:2023-02-14 Accepted:2023-04-17 Online:2024-05-08 Published:2023-08-28
  • Contact: Sun Hongyu, MD, Professor, Department of School of Clinical Medicine, Southwest Medical University, Luzhou 646000, Sichuan Province, China; Department of Basic Center Laboratory, General Hospital of Western Theater Command, Chengdu 610083, Sichuan Province, China; Sichuan Provincial Key Laboratory of Pancreatic Injury and Repair, Chengdu 610083, Sichuan Province, China
  • About author:Dong Hongfei, Master, Attending physician, Department of Burns and Plastic Surgery, General Hospital of Western Theater Command, Chengdu 610083, Sichuan Province, China; Department of School of Clinical Medicine, Southwest Medical University, Luzhou 646000, Sichuan Province, China
  • Supported by:
    General Program of National Natural Science Foundation of China, No. 81772001 (to SHY); Series Study on Graded Treatment of Abdominal Trauma and Organ Function Repair, No. 2019LH04 (to SHY); Incubation Project of Hospital Management Project of General Hospital of Western Theater Command, No. 2021-XZYG-C36 (to HX)

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摘要：


文题释义：

胎盘间充质干细胞：是从胎儿胎盘组织中分离培养获得的一种间充质干细胞，由于细胞来源为废弃的胎盘组织，所以具有组织来源丰富、无创伤、伦理限制少的优点。此外，胎盘间充质干细胞还具有良好的增殖、分化与免疫调节能力。
巨噬细胞极化：巨噬细胞在不同刺激因子诱导下，将会改变其表型，表现出多样化的功能，这个过程称为巨噬细胞极化。在创面愈合过程中，巨噬细胞对组织纤维化和瘢痕形成有重要作用，可以通过调控巨噬细胞极化从而促进伤口愈合和组织修复。


背景：目前已有多种间充质干细胞被证实具有促进创面修复的作用，但胎盘间充质干细胞是否可促进急性皮肤创面愈合目前尚缺乏相关研究。

目的：探讨胎盘间充质干细胞移植对大鼠急性皮肤损伤愈合的影响。
方法：20只SD大鼠采用随机数字表法分为PBS组、干细胞组，每组10只。所有大鼠建立全层皮肤缺损模型，PBS组、干细胞组于建模后即刻和第8天在创面及创缘分别注射PBS、胎盘间充质干细胞。建模后即刻及2，4，6，8，10，12，14 d观察创面愈合情况，在14 d时取大鼠创面处皮肤组织，进行苏木精-伊红染色、Masson染色、免疫组织化学染色及免疫荧光染色。

结果与结论：①各组大鼠创面均随治疗时间延长而缩小，干细胞组14 d时创面愈合率、创面上皮化率高于PBS组(P < 0.01)，创面挛缩比率低于PBS组(P < 0.01)；②苏木精-伊红染色结果显示，干细胞组皮肤创面修复优于PBS组，创面上皮化程度更高，胶原纤维形态更接近正常皮肤；③Masson染色结果显示，与PBS组相比，干细胞组皮肤创面组织中胶原纤维明显增多且粗大，新生组织内胶原纤维含量更多(P < 0.01)；④免疫组化染色显示，干细胞组新生毛细血管数量多于PBS组(P < 0.01)，而肿瘤坏死因子α与白细胞介素 6的表达低于PBS组(P < 0.01)；⑤免疫荧光染色显示，干细胞组新生创面内的M2型巨噬细胞数多于PBS组(P < 0.01)，M1型巨噬细胞数少于PBS组(P < 0.01)。结果表明，胎盘间充质干细胞可加速皮肤创面修复、促进创面上皮化、减轻创面挛缩，可能与促进创面内毛细血管新生、调节胶原纤维生成、抑制炎症、调控巨噬细胞向M2型极化有关。

https://orcid.org/0000-0002-4315-8145 (董鸿斐) 

中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程

关键词: 间充质干细胞, 胎盘, 创面修复, 巨噬细胞极化, 皮肤, 血管新生

Abstract: BACKGROUND: Currently, a variety of mesenchymal stem cells have been confirmed to have the effect of promoting wound repair, but there is still a lack of relevant research on whether placenta-derived mesenchymal stem cells can promote acute skin wound healing.
OBJECTIVE: To investigate the effect of placenta-derived mesenchymal stem cell transplantation on the healing of acute skin wound in rats.
METHODS: Twenty SD rats were divided into PBS group and stem cell group by the random number table method, with 10 rats in each group. All rats were selected to establish a full-thickness skin defect model. In the PBS group and stem cell group, PBS buffer and placenta-derived mesenchymal stem cells were immediately injected on the wound surface and wound margin immediately and on day 8 after modeling. The wound healing was observed immediately and on days 2, 4, 6, 8, 10, 12, and 14 after modeling. The skin tissue of the wound surface was taken on day 14 and treated with hematoxylin-eosin staining, Masson staining, immunohistochemical staining and immunofluorescence staining. 
RESULTS AND CONCLUSION: (1) The wound surface of the rats in each group decreased with the prolongation of treatment time. The wound healing rate and wound epithelization rate of the stem cell group at 14 days were higher than those of the PBS group (P < 0.01), and the wound contracture rate was lower than that of the PBS group (P < 0.01). (2) The results of hematoxylin-eosin staining showed that the skin wound healing of the stem cell group was better than that of the PBS group; the degree of wound epithelization was higher, and the morphology of collagen fibers was close to that of normal skin. (3) Masson staining results showed that compared with the PBS group, collagen fibers in the skin wound tissue of the stem cell group were significantly increased and thicker, and the content of collagen fibers in the new tissue was significantly higher than that of the PBS group (P < 0.01). (4) Immunohistochemical staining showed that the number of new capillaries in the stem cell group was higher than that in the PBS group (P < 0.01), while the expressions of tumor necrosis factor-α and interleukin-6 were lower than those in the PBS group (P < 0.01). (5) Immunofluorescence staining showed that the number of M2 macrophages in the new wounds of the stem cell group was higher than that of the PBS group (P < 0.01), while the number of M1 macrophages was less than that in the PBS group (P < 0.01). These findings indicate that placenta-derived mesenchymal stem cells can accelerate skin wound healing, promote wound epithelization, and reduce wound contracture, which may be related to the promotion of capillary angiogenesis, regulation of collagen fiber production, inhibition of inflammation, and regulation of macrophage polarization to M2 type.

Key words: mesenchymal stem cell, placenta, wound healing, macrophage polarization, skin, angiogenesis

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