Reprogrammed cardiopulmonary progenitor cell derived exosomes alleviate acute lung injury

Cardiopulmonary progenitors (CPPs) have been reported to be essential for mouse heart and lung morphogenesis. However, the function of CPPs in human embryogenesis is unknown and it is difficult to obtain human CPPs for research. Here, we found that CPPs exist in the human Carnegie stage 12 (CS12) embryo by analyzing single-cell RNA sequence data from GSE157329. Induced CPPs (iCPPs) generated from human fibroblasts by reprogramming with four lentiviral Gli1, Isl1, Wnt2, and Tbx5. These iCPPs exhibited the morphology and growth properties of iPSC cells, expressed CPPs marker genes. Transcription analysis of iCPPs, showed iCPPs contributed to heart and lung development. In addition, iCPPs could differentiate into multiple lineage cells with specific differentiation medium. Moreover, iCPPs derived exosomes alleviated mouse acute lung injury through promoting angiogenesis and suppressing inflammation. These data demonstrated that iCPPs provided a source of human CPPs, may act as a potential treatment for cardiopulmonary related diseases.