中国组织工程研究

中国组织工程研究 ›› 2021, Vol. 25 ›› Issue (1): 73-77.doi: 10.3969/j.issn.2095-4344.2143

• 脂肪干细胞 adipose-derived stem cells • 上一篇    下一篇

人脂肪间充质干细胞对异种小鼠间皮肤移植的免疫调节作用

华  红1，解童玲2，郝贵亮3   

  1. 1青岛市中医医院(市海慈医院)检验科，山东省青岛市   266000；青岛市妇女儿童医院，2呼吸科，3检验科，山东省青岛市   266000
  • 收稿日期:2019-12-09 修回日期:2019-12-12 接受日期:2020-01-17 出版日期:2021-01-08 发布日期:2020-11-19
  • 通讯作者: 郝贵亮，硕士，主管检验师，青岛市妇女儿童医院检验科，山东省青岛市 266000
  • 作者简介:华红，女，1979年生，山东省青岛市人，汉族，主管检验师，主要从事临床检验研究。

Immunomodulatory effect of human adipose derived mesenchymal stem cells on skin transplantation between different mouse strains

Hua Hong1, Xie Tongling2, Hao Guiliang3   

  1. 1Medical Laboratory, Qingdao Traditional Chinese Medicine Hospital, Qingdao 266000, Shandong Province, China; 2Department of Respiratory Medicine, 3Medical Laboratory, Qingdao Women and Children’s Hospital, Qingdao 266000, Shandong Province, China
  • Received:2019-12-09 Revised:2019-12-12 Accepted:2020-01-17 Online:2021-01-08 Published:2020-11-19
  • Contact: Hao Guiliang, Master, Laboratorian in charge, Medical Laboratory, Qingdao Women and Children’s Hospital, Qingdao 266000, Shandong Province, China
  • About author:Hua Hong, Laboratorian in charge, Medical Laboratory, Qingdao Traditional Chinese Medicine Hospital, Qingdao 266000, Shandong Province, China

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摘要：

文题释义：
脂肪间充质干细胞：是一种来源于脂肪组织，具有自我复制和多向分化潜能的成体干细胞，其高表达CD105、CD29、CD90等间充质干细胞共性表面分子，不表达CD34和CD45等表面分子，具有较低的免疫原性和较强的抑制免疫排斥作用。
皮肤移植动物模型：通过外科手术方法将一种动物的皮肤移植到另一种不同种系动物的身上，可快速有效建立皮肤移植免疫排斥动物模型。

背景：皮肤移植是治疗大面积烧烫伤最有效的方法之一，如何有效抑制异体皮肤移植后的免疫排斥反应，是目前亟待解决的问题。
目的：探讨人脂肪间充质干细胞对异种小鼠间皮肤移植免疫调节作用的影响。
方法：取抽脂减肥术后人脂肪组织分离出人脂肪间充质干细胞并培养至第3代，将60只2-4 d龄ICR小鼠随机分为4组，取其皮肤移植至C57BL/6 小鼠背部建立皮肤移植免疫排斥模型，术后30 min内通过尾静脉将PBS(PBS组)和5×104，10×104，20×104个人脂肪间充质干细胞(脂肪间充质干细胞低、中、高剂量组)注射至受体小鼠体内，记录皮肤存活时间；术后第7天每组随机取5只小鼠，分离出脾脏及血清，采用RT-PCR及ELISA法检测白细胞介素10、肿瘤坏死因子α、干扰素γ水平，取移植部位皮肤制作病理切片观察淋巴细胞浸润情况。
结果与结论：①与PBS组比较，脂肪间充质干细胞低剂量组皮肤存活时间延长但差异无显著性意义(P > 0.05)；与PBS组及脂肪间充质干细胞低剂量组比较，脂肪间充质干细胞中、高剂量组皮肤存活时间均延长(P < 0.01)，中剂量组与高剂量组间差异无显著性意义(P > 0.05)；②与PBS组比较，脂肪间充质干细胞低、中、高剂量组脾脏中肿瘤坏死因子α和干扰素γ的相对表达量均明显降低(P < 0.05)；③与PBS组比较，脂肪间充质干细胞低、中、高剂量组血清中肿瘤坏死因子α和干扰素γ水平均降低(P < 0.05)，脂肪间充质干细胞中、高剂量组白细胞介素10水平升高(P < 0.05)；④结果表明，适当剂量的人脂肪间充质干细胞可以明显延长异种小鼠间移植皮肤的存活时间，与其调节受体小鼠体内相关免疫因子的表达有关。
https://orcid.org/0000-0002-4492-1667(郝贵亮)

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: 人脂肪间充质干细胞, 异种, ICR小鼠, C57BL/6 小鼠, 皮肤移植, 免疫排斥

Abstract:

BACKGROUND: Skin transplantation is one of the most effective methods for treating large-area burns. How to effectively suppress the immune rejection after allogeneic skin transplantation is a problem that needs to be solved urgently.

OBJECTIVE: To investigate the effect of human adipose derived mesenchymal stem cells (hADSCs) on the immunoregulation of skin grafts in different strains of mice.  
METHODS:  Isolated hADSCs were cultured to the 3rd generation. Sixty ICR neonatal mice, 2-4 days of age, were randomly divided into four groups (n=15). The skin tissues of ICR neonatal mice were transplanted into adult C57BL/6 mice to establish a different strain of mouse skin graft immune rejection model. PBS and low dose (5×104), medium dose (10×104), high dose (20×104) hADSCs were injected into the model mice through tail vein, and the survival time of transplanted skin in each group was recorded. On the 7th day after operation, five mice from each group were randomly selected to remove their spleen and serum, and the expression of immune factors interleukin-10, tumor necrosis factor-α and interferon-γ were detected by RT-PCR and ELISA respectively. The transplanted part of the skin was taken to make pathological sections for observing the infiltration of lymphocytes.   
RESULTS AND CONCLUSION: Compared with the PBS group, the survival time of the skin was prolonged in the low dose hADSCs group; however, there was no significant difference between the two groups (P > 0.05). Compared with the PBS and low dose hADSCs groups, the survival time of the skin was significantly increased in the medium and high dose groups (P < 0.01), and no significant difference was found between the medium and high dose groups (P > 0.05). Compared with the PBS group, the relative expression of tumor necrosis factor-α and interferon-γ in the spleen and serum was significantly decreased in the low, medium and high dose hADSCs groups (P < 0.05), whereas the level of interleukin-10 was significantly elevated in the medium and high dose hADSCs groups (P < 0.05). To conclude, the appropriate dose of hADSCs can significantly prolong the survival time of transplanted skin between different strains of mice, by regulating the expression of related immune factors in the recipient mice.

Key words: human adipose derived mesenchymal stem cells, different strains, ICR mice, C57BL/6 mice, skin graft, immunological rejection

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