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

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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

(1x106; 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 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) 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.

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