人脐带间充质干细胞对T细胞活化介导的肺动脉平滑肌细胞增殖抑制及机制研究

吴西军; 刘庆; 刘俊峰; 杨小燕; 何志旭

doi:10.16016/j.1000-5404.201906045

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人脐带间充质干细胞对T细胞活化介导的肺动脉平滑肌细胞增殖抑制及机制研究

基础医学 | 更新时间：2026-01-09

- 人脐带间充质干细胞对T细胞活化介导的肺动脉平滑肌细胞增殖抑制及机制研究
- Inhibitory effect and mechanism of human umbilical cordmesenchymal stem cells on T cell activation-mediated proliferation of pulmonary artery smooth muscle cells
- 第三军医大学学报 2019年41卷第22期页码：2174-2180
- 作者机构：
  
  1.550004 贵阳，贵州医科大学:细胞工程生物医药技术国家地方联合工程实验室，贵州省再生医学重点实验室
  2.550004 贵阳，贵州医科大学:中国医学科学院成体干细胞转化研究重点实验室
  3.550004 贵阳，贵州医科大学:免疫学教研室
  4.550004 贵阳，贵州医科大学:附属医院呼吸内科
  5.550004 贵阳，贵州医科大学:附属医院儿童血液肿瘤科
- 作者简介：
  
  [何志旭, E-mail:hzx@gmc.edu.cnHE Zhixu, E-mail: hzx@gmc.edu.cn
- 基金信息：
  
  国家自然科学基金面上项目(81871313);中国医学科学院中央级公益性科研院所基本科研业务费专项资金(2017PT31042);中国医学科学院中央级公益性科研院所基本科研业务费专项资金(2018PT31048);贵州省“十二五”计划重大科技专项[黔教合重大专项(2013-021);贵阳市-贵州医科大学联合基金项目(筑科合同(2015)001-03)
- DOI：10.16016/j.1000-5404.201906045
  中图分类号： R322.121;R329.2;R363.22
- 收稿：2019-06-08，
  
  修回：2019-09-22，
  
  纸质出版：2019-11-30
- 稿件说明：
移动端阅览
吴西军, 刘庆, 刘俊峰, 等. 人脐带间充质干细胞对T细胞活化介导的肺动脉平滑肌细胞增殖抑制及机制研究[J]. 第三军医大学学报, 2019,41(22):2174-2180.

Xijun WU, Qing LIU, Junfeng LIU, et al. Inhibitory effect and mechanism of human umbilical cordmesenchymal stem cells on T cell activation-mediated proliferation of pulmonary artery smooth muscle cells[J]. Journal of Third Military Medical University, 2019, 41(22): 2174-2180.
吴西军, 刘庆, 刘俊峰, 等. 人脐带间充质干细胞对T细胞活化介导的肺动脉平滑肌细胞增殖抑制及机制研究[J]. 第三军医大学学报, 2019,41(22):2174-2180. DOI： 10.16016/j.1000-5404.201906045.

Xijun WU, Qing LIU, Junfeng LIU, et al. Inhibitory effect and mechanism of human umbilical cordmesenchymal stem cells on T cell activation-mediated proliferation of pulmonary artery smooth muscle cells[J]. Journal of Third Military Medical University, 2019, 41(22): 2174-2180. DOI： 10.16016/j.1000-5404.201906045.

摘要

目的

阐释人脐带间充质干细胞(human umbilical cord mesenchymal stem cells，hu-MSCs)抑制T淋巴细胞活化介导的肺动脉平滑肌细胞(pulmonary artery smooth muscle cells，PASMCs)增殖的作用及可能的调节机制。

方法

复苏并培养hu-MSCs和大鼠来源的PASMCs、T细胞，将实验分为PASMCs对照组、T细胞刺激组(PASMCs+T淋巴细胞)、MSC干预组(PASMCs+T淋巴细胞+MSC)、英夫利西单抗干预组(PASMCs+T淋巴细胞+英夫利西单抗)、TNF-α刺激组(PASMCs+T淋巴细胞+MSC+TNF-α)。通过荧光分光光度计、RT-qPCR、倒置荧光显微镜观察等方法研究钙调磷酸酶、T淋巴细胞核因子的变化。

结果

T淋巴细胞刺激组TNF-α浓度明显升高(

0.01)；MSCs与英夫利西单抗均能明显降低其TNF-α浓度(

0.01)。与单纯PASMCs对照组比较

T淋巴细胞刺激组PASMCs的增殖能力明显增强(

0.01)，胞浆中游离钙离子的浓度明显升高(

0.01)，胞内CaN的表达(

0.01)和活性(

0.01)均显著上调，NFATc2的表达和活性亦显著上调(

0.01)；与T淋巴细胞刺激组相比，MSCs干预组、英夫利西单抗干预组PASMCs的增殖被明显抑制(

0.01)

胞浆中游离钙离子的浓度均明显下降(

0.01)，胞内CaN的表达(

0.01)和活性(

0.01)均显著下调，NFATc2的表达(

0.01)和活性亦下调；外源TNF-α可有效逆转MSC的干预作用，其作用与T淋巴细胞刺激组几乎相当。

结论

hu-MSCs可以通过改变CaN、NFATc2的表达和活化状态，抑制T淋巴细胞活化

抑制炎症因子TNF-α导致的PASMCs增殖。

Abstract

Objective

To investigate the inhibitory effect of human umbilical cord mesenchymal stem cells (hu-MSCs) on T lymphocyte activation-mediated proliferation of pulmonary artery smooth muscle cells (PASMCs) and explore the possible regulatory mechanism.

Methods

Cultured rat PASMCs were stimulated with activated T lymphocytes with subsequent exposures to hu-MSCs

infliximab

or both hu-MSCs and tumor necrosis factor-α (TNF-α). The changes in calcineurin and T lymphoid nuclear factor in the cell cultures were observed using fluorescence spectrophotometer

RT-qPCR and inverted fluorescence microscopy.

Results

Among all the treatments

stimulation with activated T lymphocytes alone resulted in the highest concentration of TNF-α in the supernatant of PASMC culture (

0.01). Co-culture with Hu-MSCs and treatment with infliximab both significantly decreased TNF-α concentration in PASMCs stimulated with activated T lymphocytes (

0.01). Stimulation with T lymphocytes significantly enhanced the proliferative activity of the PASMCs

increased Ca

concentration in the cytoplasm

and up-regulated the expression and activity of intracellular CaN and NFATc2. Co-culture with Hu-MSCs and treatment with infliximab significantly suppressed the proliferation of PASMCs stimulated with T lymphocytes

decreased the concentration of Ca

in the cytoplasm

and lowered both the expression and activity of intracellular CaN and NFATc2. Exogenous TNF-α obviously reversed the effects of Hu-MSC on the PASMCs

and produced responses similar to T-lymphocyte stimulation in the PASMCs.

Conclusion

Hu-MSCs can promote the proliferation of PASMCs by modulating the expression and activation of CaN and NFATc2 to inhibit the activation of T lymphocytes and the PASMCs proliferation induced by inflammatory factor TNF-α.

关键词

Keywords

references

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