肺部疾病 - 间质干细胞

人类胚胎干细胞衍生的间质干细胞的细胞存活率和旁分泌能力的提高促进了肺动脉高压的治疗潜力

张跃林,* 廖松岩,* 杨默,†‡ 梁晓婷,* 潘明伟,* 黄志贤,§ 王俊文,∥ 周中军,∥ 张顺景,§ 李全能,# 谢宏发,*,** 和连启洲*,**†† 

*香港大学医学部心脏科,香港。†南方医科大学,‡香港大学李嘉诚医学院药理和药学系,香港§吉隆坡MAKNA-HUKM癌症研究所,∥香港大学生物化学系,香港。#National University of Singapore, Singapore.**香港大学李嘉诚医学院心、脑、荷尔蒙及健康老化研究中心,香港。††香港大学李嘉诚医学院眼科研究所,香港。 

Although transplantation of adult bone marrow mesenchymal stem cells (BM-MSCs) holds promise in the treatment for pulmonary arterial hypertension (PAH), the poor survival and differentiation potential of adult BM-MSCs have limited their therapeutic efficiency. Here, we compared the therapeutic efficacy of human embryonic stem cell-derived MSCs (hESC-MSCs) with adult BM-MSCs for the treatment of PAH in an animal model. One week following monocrotaline (MCT)-induced PAH, mice were randomly assigned to receive phosphate-buffered saline (MCT group); 3.0×10(6) human BM-derived MSCs (BM-MSCs group) or 3.0×10(6) hESC-derived MSCs (hESC-MSCs group) via tail vein injection. At 3 weeks post-transplantation, the right ventricular systolic pressure (RVSP), degree of RV hypertrophy, and medial wall thickening of pulmonary arteries were lower=, and pulmonary capillary density was higher in the hESC-MSC group as compared with BM-MSC and MCT groups (all p < 0.05). At 1 week post-transplantation, the number of engrafted MSCs in the lungs was found significantly higher in the hESC-MSC group than in the BM-MSC group (all p < 0.01). At 3 weeks post-transplantation, implanted BM-MSCs were undetectable whereas hESC-MSCs were not only engrafted in injured pulmonary arteries but had also undergone endothelial differentiation.

此外,对hESC-MSC-和BM-MSC-条件培养基的蛋白质分析显示了不同的旁分泌能力。将这些因子分类为生物过程显示,来自hESC-MSCs的分泌因子优先参与早期胚胎发育和组织分化,特别是血管形态的形成。我们的结论是,在治疗PAH方面,hESC-MSCs的细胞存活率和旁分泌能力的提高比BM-MSCs具有更好的疗效。