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


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Abstract

Pulmonary hypertension (PH) is a devastating cardiopulmonarydisorder, which often results in right heart failure. In spite of recentadvancements in the pharmacotherapy of pulmonary hypertension, the mortalityrate has not been significantly reduced. Recently stem cell therapy has gainedmore attention for the treatment of cardiopulmonary diseases. Despite thepromising results shown by bone marrow derived stem cells in attenuating right heartfailure 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 inattenuating the progression of PH. Monocrotaline(MCT) at a 50 mg/kg dose was injected to eight-week old male Sprague-Dawleyrats to induce PH. Four weeks post MCT injection; animals developed PH withelevated 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 malerat) were characterized using flow cytometry (CD44+, CD90+,CD34- and CD45-) and their differentiation to adipocytewas confirmed by Oil Red O staining. ADSCs(1x106; passage 2-4) were injected through the jugular vein, 14 dayspost MCT injection. After 2 weeks followingADSC 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 enddiastolic pressure (RVEDP) and ±dP/dT associated with PH were attenuatedsignificantly in ADSC treated MCT animals. An additional group of animals received onlythe ADSC conditioned media (CM) from 1x106 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) wassignificantly reduced. Further, the RVEDPand ± dP/dT were also significantly reduced in CM treated MCT animals. Collectively, either ADSC or conditioned mediaalone can attenuate the progression of PH, which suggest that paracrine-like substancesmay be responsible for the beneficial effects observed and may be considered asa potential therapeutic alternative for the treatment of right heart failure.

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