基于间充质干细胞的血管紧张素转换酶2在博来霉素诱导的急性肺损伤大鼠治疗中的应用
Mesenchymal stem cell-based angiotensin-converting enzyme 2 in treatment of acute lung injury rat induced by bleomycin.
作者信息
Gao Fengying, Li Qian, Hou Lili, Li Zhuozhe, Min Fang, Liu Zhenwei
机构信息
1Department of Respiratory Medicine, Shanghai JianGong Hospital, Shanghai, P. R. China.
出版信息
Exp Lung Res. 2014 Oct;40(8):392-403. doi: 10.3109/01902148.2014.938200. Epub 2014 Aug 28.
BACKGROUND
Acute lung injury (ALI) is a high incidence disease with no effective therapeutic method (mortality rate > 40%). The aim of this study was to find a new and effective therapeutic method for ALI.
METHODS
After the isolation of human umbilical cord mesenchymal stem cells (HUMSCs) from cesarean fetus, we transfected the HUMSCs with Lenti-ACE2 (angiotensin-converting enzyme 2) viral particles. Then we evaluated the therapeutic effect of HUMSCs harboring ACE2 on ALI, which induced by bleomycin (BLM) in rat model.
RESULTS
Our results showed that HUMSCs harboring ACE2 could attenuate ALI degree through reducing pulmonary inflammatory infiltration and degree of vascular permeability, repressing the mRNA level of pro-inflammatory cytokines, activating the mRNA level of anti-inflammatory cytokines and ACE2. Besides, results also demonstrated that HUMSCs harboring ACE2 gene had higher therapeutic effects to ALI than the single factor of HUMSCs or ACE2.
CONCLUSIONS
This research provided clues for the development of effective therapeutic methods to ALI using stem cell transplantation and gene therapy.
背景
急性肺损伤（ALI）是一种发病率高且尚无有效治疗方法（死亡率>40%）的疾病。本研究的目的是寻找一种治疗ALI的新的有效方法。
方法
从剖宫产胎儿中分离出人脐带间充质干细胞（HUMSCs）后，用慢病毒血管紧张素转换酶2（Lenti-ACE2）颗粒转染HUMSCs。然后我们评估了携带ACE2的HUMSCs对博来霉素（BLM）诱导的大鼠ALI模型的治疗效果。
结果
我们的结果表明，携带ACE2的HUMSCs可通过减少肺部炎症浸润和血管通透性程度、抑制促炎细胞因子的mRNA水平、激活抗炎细胞因子和ACE2的mRNA水平来减轻ALI程度。此外，结果还表明，携带ACE2基因的HUMSCs对ALI的治疗效果高于HUMSCs或ACE2单一因素。
结论
本研究为利用干细胞移植和基因治疗开发ALI有效治疗方法提供了线索。
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