Adipose-derived regenerative cell therapy inhibits the progression of monocrotaline-induced pulmonary hypertension in rats

article i nfo Aims: Functional and structural changes in pulmonary vasculature characterize pulmonary arterial hypertension (PAH) and the prognosis of advanced PAH remains poor despite progress in pharmacotherapy. Adipose-derived regenerative cells (ADRCs) promote cell regeneration at pathological sites and comprise a novel therapy for ail- ments of various organs. We investigated the effects of ADRC therapy in rat models of monocrotaline (MCT)-in- duced pulmonary hypertension (PH) and the underlying mechanisms. Mainmethods:RatswereassignedtoControl andMCT groupswithoutandwith (M/A)intravenoustransfusionof seven million ADRCs on day 7. We echocardiographically evaluated pulmonary hypertension as pulmonary ar- tery flow acceleration time (PAAT) and deceleration (PADc). Right ventricular (RV) systolic pressure was mea- sured by catheterization on day 28 and then pathological changes in pulmonary vessels were assessed. We analyzed PAH-associated gene expression on day 14 using real-time RT-PCR. Key findings: Echocardiography and RV catheterization showed that ADRC therapy inhibited PH development (assessedasPAAT,PADc,andRVsystolicpressure)atday28(MCTvs.M/A,Pb 0.05).Pulmonaryvascularremod- eling was also inhibited (vessel wall thickness: MCT vs. M/A, P b 0.01). Messenger RNA levels of endothelin (ET) A and B receptors, ET-1 and transforming growth factor (TGF)-β increased in the lungs by MCT were suppressed by ADRCs (MCT vs. M/A, P b 0.05). Significance: The development of PH was inhibited by ADRCs through suppressing changes in the expression of genes associated with ET and TGF-β systems. We believe that ADRC therapy could serve as a novel strategy for treating PH.