Mesenchymal Stem Cells Conditioned Media Suppress Inflammation Associated Over-proliferation of Pulmonary Artery Smooth Muscle Cells in a Rat Model of Pulmonary Hypertension

Authors:
Liu JF, Han Z, Han ZC, HeZX
In:
Source: Other
Publication Date: (2014)
Issue: 20(8): 3411-3439
Cells used in publication:
Mesenchymal stem cell (MSC), human
Species: human
Tissue Origin: bone marrow
SMC, pul.artery (PASMC), human
Species: human
Tissue Origin: artery
Culture Media:
Abstract
Inflammation associated over-proliferation of pulmonary artery smooth muscle cells (PASMCs) is considered to be involved in the pathogenesis of pulmonary hypertension (PH). Even though administration of mesenchymal stem cells conditioned media (MSCs-CM) could improve PH, the exact mechanism is not completely clear. Here we aimed to determine that MSCs-CM suppress over-proliferation of PASMCs in PH by the immunoregulation. By administration of MSCs-CM in monocrotaline (MCT) induced PH rats, and an in vitro co-culture system comprised of PASMCs and activated T cells, we assessed the therapeutic effects of MSCs-CM on PH and the changes of correlate factors including TNF-a, ncalcineurin (CaN) and nuclear factor of activated T-cells (NFAT). The results indicated that MSCs-CM could suppress the production of TNF-a in MCT induced PH or co-culture system, and then down-regulate the expression of CaN and NFATc2 in PASMCs, suppress the CaN activity and NFATc2 activation, thus inhibit the over-proliferation of PASMCs, and finally improve the abnormality of hemodynamics and pulmonary histology in MCT induced PH. In conclusion, our findings have suggested that administration of MSCs-CM could suppress inflammatory associated over-proliferation of PASMCs via immunosuppressive effects in PH.