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

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.

[Effects of nitric oxide on form-deprivation myopia in chicks].

OBJECTIVE: To construct a chick model of form-deprivation myopia (FDM) to investigate the effect of nitric oxide (NO) on FDM. METHODS: FDM was induced in 60 one-day white leghorn chicks. They were divided into group A and B. One eye was covered randomly, and the other served as control. In each week of the experimental period, the retinoscopic refraction was performed, and the axial length was measured with A-mode ultrasound. The NO concentration of retina and choroid from the control and the experimental eyes was measured using NO detection kit. Change in the expression of iNOS mRNA was measured by RT-PCR. The activity of iNOS was analyzed with immunohistochemistry. RESULTS: Form-deprivation eyes were significantly more myopic than the controls, and the axial length of occluded eyes was significantly longer than that of the controls. Unocclusion attenuated the development of myopia and inhibited the axial elongation. Form-deprivation reduced the NO concentration ,the immunoreactivity of iNOS, and the expression of iNOS mRNA. The gradual restoration of normal vision was found after uncovering the eyes. But the expression of iNOS mRNA was significantly higher than that of the controls at the first week after the unocclusion. CONCLUSION: Form-deprivation can construct an animal model of myopia. FDM is reversible before the chicks were mature. NO may be involved in the form of FDM.