广州医科大学Xi-yong Yu团队近期取得重要工作进展，他们研究提出，诱导的心肺祖细胞来源的外泌体可减轻小鼠急性肺损伤。相关研究成果2024年4月8日在线发表于《中国药理学报》杂志上。

据介绍，心肺祖细胞（CPP）是一个小的细胞亚群，在胚胎发育过程中通常与心肺形态发生有关，但在出生后完全消退。这一事实为治疗肺和心脏都受到损害的肺心病（PHD）提供了可能。目前迫切需要一个可靠的CPP来源。

研究人员将人类心脏成纤维细胞（HCF）重新编程为CPP样细胞（或诱导的CPP，iCPP），并评估了iCPP来源的外泌体对急性肺损伤（ALI）的治疗潜力。通过过表达GLI1、WNT2、ISL1和TBX5（GWIT）在第3代原发性HCF中产生iCPP。外泌体是从第6-8代GWIT-iCPP的培养基中分离出来的。通过气管内滴注LPS建立小鼠ALI模型。LPS滴注4小时后，用GWIT-iCPP来源的外泌体（5 × 10⁹, 5 × 10¹⁰个微粒/mL）。

研究人员发现GWIT-iCPP在体外可以分化为细胞谱系，如心肌细胞样细胞、内皮细胞、平滑肌细胞和肺泡上皮细胞。转录分析显示GWIT-iCPP具有心脏和肺部发育的潜力。气管内滴注iCPP来源的外泌体通过减轻肺部炎症、促进内皮功能和恢复毛细血管内皮细胞和上皮细胞屏障，剂量依赖性地减轻LPS诱导的小鼠急性肺损伤。

总之，该研究为预防和治疗心肺损伤，特别是肺损伤提供了一种潜在的新方法，并为药物筛选提供了一个新的细胞模型。

附：英文原文

Title: Exosomes derived from induced cardiopulmonary progenitor cells alleviate acute lung injury in mice

Author: Xia, Luo-xing, Xiao, Ying-ying, Jiang, Wen-jing, Yang, Xiang-yu, Tao, Hua, Mandukhail, Safur Rehman, Qin, Jian-feng, Pan, Qian-rong, Zhu, Yu-guang, Zhao, Li-xin, Huang, Li-juan, Li, Zhan, Yu, Xi-yong

Issue&Volume: 2024-04-08

Abstract: Cardiopulmonary progenitor cells (CPPs) constitute a minor subpopulation of cells that are commonly associated with heart and lung morphogenesis during embryonic development but completely subside after birth. This fact offers the possibility for the treatment of pulmonary heart disease (PHD), in which the lung and heart are both damaged. A reliable source of CPPs is urgently needed. In this study, we reprogrammed human cardiac fibroblasts (HCFs) into CPP-like cells (or induced CPPs, iCPPs) and evaluated the therapeutic potential of iCPP-derived exosomes for acute lung injury (ALI). iCPPs were created in passage 3 primary HCFs by overexpressing GLI1, WNT2, ISL1 and TBX5 (GWIT). Exosomes were isolated from the culture medium of passage 6–8 GWIT-iCPPs. A mouse ALI model was established by intratracheal instillation of LPS. Four hours after LPS instillation, ALI mice were treated with GWIT-iCPP-derived exosomes (5×109, 5×1010 particles/mL) via intratracheal instillation. We showed that GWIT-iCPPs could differentiate into cell lineages, such as cardiomyocyte-like cells, endothelial cells, smooth muscle cells and alveolar epithelial cells, in vitro. Transcription analysis revealed that GWIT-iCPPs have potential for heart and lung development. Intratracheal instillation of iCPP-derived exosomes dose-dependently alleviated LPS-induced ALI in mice by attenuating lung inflammation, promoting endothelial function and restoring capillary endothelial cells and the epithelial cells barrier. This study provides a potential new method for the prevention and treatment of cardiopulmonary injury, especially lung injury, and provides a new cell model for drug screening.

DOI: 10.1038/s41401-024-01253-4

Source: https://www.nature.com/articles/s41401-024-01253-4