Abstract 11403: Adipose-Derived Regenerative Cell Therapy Improves Pulmonary Arterial Hypertension Through an Anti-Inflammatory Mechanism
Introduction: Pulmonary arterial hypertension (PAH) is characterized by functional and structural changes in the pulmonary vasculature. Despite the progress of pharmacotherapy, the prognosis of patients with advanced PAH remains poor. Adipose-derived regenerative cell (ADRC) therapy has recently emerged as a novel therapy for ailments of various organs, promoting cell regeneration at the site of pathology. This study investigated the efficacy of ADRC therapy on PAH using a monocrotaline (MCT)-induced PAH rat model, and explored the underlying mechanisms.
Methods: Male Wistar rats were divided into control, MCT, and MCT with ADRC transfusion (M/A) groups. Intravenous transfusion of 7х106 ADRCs was performed at one week after MCT injection in the M/A group. Pulmonary hypertension (PH) was evaluated by measuring acceleration time (AT) and deceleration (Dct) of PA flow using echocardiography. At four weeks after MCT injection, pathological changes in pulmonary vessels were assessed. Expression of genes associated with PAH was analyzed at two weeks after MCT injection by real time RT-PCR.
Results: Echocardiography showed that ADRC therapy inhibited the development of PH at day 28 (AT: MCT 20.4 ± 3.1 vs. M/A 24.0 ± 4.0, p<0.05; Dct: MCT 1474.0 ± 467.9 vs. M/A 898.6 ± 238.3, p<0.005, n=9). Histological analysis showed that pulmonary vascular remodeling induced by MCT was also inhibited by ADRC therapy (vessel wall thickness: MCT 0.44 ± 0.04 vs. M/A 0.31 ± 0.04, p<0.001, n=9). ADRCs were labeled with DiI before transfusion and the transfused cells were confirmed to exist in the lung tissue by fluorescence microscopy. MCT treatment increased mRNA levels of endothelin (ET) receptor-A, ET receptor B, ET-1 and transforming growth factor (TGF)-beta in the lung. ADRC therapy suppressed these increases in mRNA levels of ET receptor-A (MCT 1.73 vs. M/A 1.11, p<0.05, n=6), ET receptor B (MCT 2.77 vs. M/A 1.13, p<0.05, n=6), ET-1 (MCT 3.08 vs. M/A 1.41, p<0.05, n=6) and TGF-beta (MCT 3.39 vs. M/A 2.03, p<0.05, n=6).
Conclusions: ADRC therapy inhibited the development of PAH by reversing the changes in ET expression and inflammatory cytokines. These findings suggest that ADRC therapy may open a novel strategy for treating PAH.
- © 2013 by American Heart Association, Inc.