Mesenchymal stem cell-conditioned media suppresses inflammation-associated overproliferation of pulmonary artery smooth muscle cells in a rat model of pulmonary hypertension

Inflammation-associated overproliferation of pulmonary artery smooth muscle cells (PASMCs) is considered to be involved in the pathogenesis of pulmonary hypertension (PH). The administration of mesenchymal stem cell‑conditioned media (MSC‑CM) has displayed benefits in the treatment of PH, however, the exact mechanism has yet to be elucidated. The present study aimed to determine whether MSC‑CM is able to suppress overproliferation of PASMCs in PH via immunoregulation. By the administration of MSC‑CM to monocrotaline (MCT)‑induced PH rats, and the development of an in vitro co‑culture system comprised of PASMCs and activated T cells, the therapeutic effects of MSC‑CM on PH, and the changes in the expression of correlated factors, including TNF‑α, calcineurin (CaN) and nuclear factor of activated T cells (NFAT), were assessed. Immunohistochemical staining results indicated that MSC‑CM was able to significantly suppress the production of TNF‑α in MCT‑induced PH and co‑culture systems; and reverse transcription‑quantitative polymerase chain reaction results showed significant downregulation of the expression of CaN and NFATc2 in PASMCs (P<0.01). Furthermore, MSC‑CM was able to significantly suppress CaN activity and NFATc2 activation (P<0.01), thus inhibiting the overproliferation of PASMCs. Finally, MSC‑CM improved abnormalities in hemodynamics and pulmonary histology in MCT‑induced PH. In conclusion, the findings of the current study suggest that administration of MSC‑CM has the potential to suppress inflammation‑associated overproliferation of PASMCs due to its immunosuppressive effects in PH and, thus, may serve as a beneficial therapeutic strategy.