Chen Qin, Lv Lu, Zheng Chujie, Pan Huiwen, Xu Jili, Lin Jiang, Deng Zhaoqun, Qian Wei
Laboratory Center, Affiliated People's Hospital of Jiangsu University, Zhenjiang, China.
Department of Cardiothoracic Surgery, Affiliated People's Hospital of Jiangsu University, Zhenjiang, China.
Int J Stem Cells. 2022 Nov 30;15(4):395-404. doi: 10.15283/ijsc21149. Epub 2022 Feb 28.
Chronic obstructive pulmonary disease (COPD) is a common, frequently-occurring disease and poses a major health concern. Unfortunately, there is current no effective treatment for COPD, particularly emphysema. Recently, experimental treatment of COPD using mesenchymal stem cells (MSCs) mainly focused on bone marrow-derived MSCs (BM-MSCs). Human umbilical cord-derived MSCs (hUC-MSCs) have more advantages compared to BM-MSCs. However, studies on the role of hUC-MSCs in management of COPD are limited. This study sought to explore the role of hUC-MSCs and its action mechanisms in a rat model of VEGF receptor blocker SU5416-injured emphysema.
hUC-MSCs were characterized by immunophenotype and differentiation analysis. Rats were divided into four groups: Control, Control＋MSC, SU5416 and SU5416＋MSC. Rats in model group were administered with SU5416 for three weeks. At the end of the second week after SU5416 administration, model group were infused with 3×10 hUC-MSCs through tail vein. After 14 days from hUC-MSCs transplantation, rats were euthanized and data were analyzed. HE staining and mean linear intercepts showed that SU5416-treated rats exhibited typical emphysema while emphysematous changes in model rats after hUC-MSCs transplantation disappeared completely and were restored to normal phenotype. Furthermore, hUC-MSCs inhibited apoptosis as shown by TUNEL and Western blotting. ELISA and Western blotting showed hUC-MSCs rescued VEGF-VEGFR2-AKT pathway in emphysematous lungs.
The findings show that hUC-MSCs effectively repair the emphysema injury. This study provides the first evidence that hUC-MSCs inhibit apoptosis via rescuing VEGF- VEGFR2-AKT pathway in a rat model of emphysema.
慢性阻塞性肺疾病（COPD）是一种常见的多发病，是主要的健康问题。遗憾的是，目前尚无治疗COPD尤其是肺气肿的有效方法。最近，使用间充质干细胞（MSC）对COPD进行实验性治疗主要集中于骨髓来源的MSC（BM-MSC）。与BM-MSC相比，人脐带源MSC（hUC-MSC）具有更多优势。然而，关于hUC-MSC在COPD治疗中作用的研究有限。本研究旨在探讨hUC-MSC在VEGF受体阻滞剂SU5416诱导的肺气肿大鼠模型中的作用及其作用机制。
通过免疫表型和分化分析对hUC-MSC进行鉴定。将大鼠分为四组：对照组、对照+MSC组、SU5416组和SU5416+MSC组。模型组大鼠给予SU5416三周。在给予SU5416后第二周结束时，模型组通过尾静脉注入3×10的hUC-MSC。hUC-MSC移植后14天，对大鼠实施安乐死并分析数据。HE染色和平均线性截距显示，SU5416处理的大鼠呈现典型的肺气肿，而hUC-MSC移植后模型大鼠的肺气肿改变完全消失并恢复正常表型。此外，TUNEL和蛋白质印迹显示hUC-MSC抑制细胞凋亡。ELISA和蛋白质印迹显示hUC-MSC挽救了肺气肿肺组织中的VEGF-VEGFR2-AKT信号通路。
研究结果表明，hUC-MSC可有效修复肺气肿损伤。本研究首次证明，在肺气肿大鼠模型中，hUC-MSC通过挽救VEGF-VEGFR2-AKT信号通路抑制细胞凋亡。
