title: Mesenchymal stem cell-conditioned media suppresses inflammation-associated overproliferation of pulmonary artery smooth muscle cells in a rat model of pulmonary hypertension.
abstract: 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 anin vitroco-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.
authors.affiliation: Laboratory of Tissue Engineering and Stem Cells, Guiyang Medical College, Guiyang, Guizhou 550004, P.R. China; Department of Pediatrics, Affiliated Hospital of Guiyang Medical College, Guiyang, Guizhou 550004, P.R. China; Department of Pediatrics, The General Hospital of Huabei Oil Field Company, Renqiu, Hebei 062552, P.R. China.
authors.forename: Junfeng
authors.initials: J
authors.lastname: Liu
authors.affiliation: National Engineering Research Center of Cell Products, AmCellGene Co., Ltd., Tianjin 300457, P.R. China.
authors.forename: Zhibo
authors.initials: Z
authors.lastname: Han
authors.affiliation: National Engineering Research Center of Cell Products, AmCellGene Co., Ltd., Tianjin 300457, P.R. China.
authors.forename: Zhongchao
authors.initials: Z
authors.lastname: Han
authors.affiliation: Laboratory of Tissue Engineering and Stem Cells, Guiyang Medical College, Guiyang, Guizhou 550004, P.R. China; Department of Pediatrics, Affiliated Hospital of Guiyang Medical College, Guiyang, Guizhou 550004, P.R. China.
authors.forename: Zhixu
authors.initials: Z
authors.lastname: He
keywords: calcineurin; conditioned media; mesenchymal stem cells; nuclear factor of activated T cells; pulmonary hypertension; rat; tumor necrosis factor-α