Abstract 609: Potential Role Of Adipose Derived Stem Cells In Attenuating Pulmonary Hypertension

Abstract

Pulmonary hypertension (PH) is a devastating cardiopulmonary disorder, which often results in right heart failure. In spite of recent advancements in the pharmacotherapy of pulmonary hypertension, the mortality rate has not been significantly reduced. Recently stem cell therapy has gained more attention for the treatment of cardiopulmonary diseases. Despite the promising results shown by bone marrow derived stem cells in attenuating right heart failure in PH, it remains a highly invasive and laborious procedure. On the contrary, adipose derived stem cell (ADSC) presents a less complicated option. Therefore, we proposed to use ADSC in attenuating the progression of PH. Monocrotaline (MCT) at a 50 mg/kg dose was injected to eight-week old male Sprague-Dawley rats to induce PH. Four weeks post MCT injection; animals developed PH with elevated right ventricular systolic pressure (RVSP, Control: 28.65±0.40; MCT: 78.06±6.4 mmHg; n=6-8), and right ventricular hypertrophy (RVH, Control; 0.22±0.005; MCT: 0.48±0.054 [ratio, AU]; n=6-8). ADSC (isolated from inguinal fat of healthy male rat) were characterized using flow cytometry (CD44 + , CD90 + , CD34 - and CD45 - ) and their differentiation to adipocyte was confirmed by Oil Red O staining. ADSCs (1x10 6 ; passage 2-4) were injected through the jugular vein, 14 days post MCT injection. After 2 weeks following ADSC therapy, RVSP (MCT+ADSC: 55.67±8.99 mmHg; n=6-8) and RVH (MCT+ADSC: 0.32±0.062 [AU]; n=6-8) was significantly reduced. Moreover, the elevated right ventricular end diastolic pressure (RVEDP) and ±dP/dT associated with PH were attenuated significantly in ADSC treated MCT animals. An additional group of animals received only the ADSC conditioned media (CM) from 1x10 6 cells. After 2 weeks of CM administration, RVSP (MCT+CM: 42.11±4.66 mmHg; n=5) and RVH (MCT+CM: 0.29±0.020 [AU]; n=5) was significantly reduced. Further, the RVEDP and ± dP/dT were also significantly reduced in CM treated MCT animals. Collectively, either ADSC or conditioned media alone can attenuate the progression of PH, which suggest that paracrine-like substances may be responsible for the beneficial effects observed and may be considered as a potential therapeutic alternative for the treatment of right heart failure.