Tibetan umbilical cord mesenchymal stem cell exosomes improve hypoxic pulmonary hypertension by inhibiting pulmonary vascular remodeling

Abstract

Abstract Aims Pulmonary hypertension (PH) is a progressive disease that involves pulmonary vasoconstriction, pulmonary vascular remodeling, and right ventricular hypertrophy, ultimately leading to right heart failure. However, current treatments for pulmonary hypertension have several limitations. This study aims to explore the therapeutic potential of Tibetan umbilical cord mesenchymal stem cell (MSC) exosomes (exos) in treating PH, and to compare their treatment efficacy with Han Chinese umbilical cord MSC exosomes. Methods and results A rat model of hypoxic pulmonary hypertension (HPH) was established in vivo to study the effects of exosomes derived from human umbilical cord mesenchymal stem cell (hUCMSC) supernatant. Additionally, an in vitro model of hypoxia-induced pulmonary artery smooth muscle cell (PASMC) injury was established. The therapeutic effects of Tibetan-MSC-exo and Han-MSC-exo on HPH were investigated using various techniques such as immunohistochemistry, Western blotting, an EdU cell proliferation kit, and Transwell assay. The results demonstrated that Tibetan-MSC-exo had a more significant impact in attenuating pulmonary vascular remodeling and right ventricular hypertrophy (RVH) in HPH rats compared to Han-MSC-exo. In cell culture experiments, Tibetan-MSC-exo showed a stronger inhibition of hypoxia-induced PASMC proliferation and migration. Furthermore, this study revealed that Tibetan-MSC-exo downregulated TGFβ1 expression in HPH rats and hypoxia-induced PASMCs to a greater extent than Han-MSC-exo. It was also observed that overexpression of the TGFβ1 gene diminished the therapeutic effects of both Tibetan-MSC-exo and Han-MSC-exo on hypoxic injury. Conclusion In this study, we demonstrated that Tibetan-MSC-exo exhibited a superior effect compared to Han-MSC-exo in treating HPH. Furthermore, we confirmed that this mechanism was associated with the down-regulation of the TGFβ1/p-Smad2/3 pathway.