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논문 기본 정보

자료유형
학술저널
저자정보
Park Ji Hye (Pusan National University) Kim Hyeok (The Catholic University of Korea) Moon Hyung Ryong (Pusan National University) 박봉우 (가톨릭대학교) Park Jae-Hyun (The Catholic University of Korea) Sim Woo-Sup (The Catholic University of Korea) Kim Jin-Ju (The Catholic University of Korea) Lim Hye Ji (Pusan National University) Kim Yeon-Ju (Pusan National University) 지승택 (부산대학교) 장웅비 (부산대학교) Rethineswaran Vinoth Kumar (Pusan National University) Van Le Thi Hong (Pusan National University) Giang Ly Thanh Truong (Pusan National University) Yun Jisoo (Pusan National University) Ha Jong Seong (Pusan National University) Ban Kiwon (City University of Hong Kong) Chung Hae Young (Pusan National University) Baek Sang Hong (The Catholic University of Korea) Park Hun-Jun (The Catholic University of Korea) 권상모 (부산대학교)
저널정보
대한생화학·분자생물학회 Experimental and Molecular Medicine Experimental and Molecular Medicine 제53권
발행연도
2021.9
수록면
1 - 14 (14page)
DOI
10.1038/s12276-021-00676-x

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Stem cell-based therapies with clinical applications require millions of cells. Therefore, repeated subculture is essential for cellular expansion, which is often complicated by replicative senescence. Cellular senescence contributes to reduced stem cell regenerative potential as it inhibits stem cell proliferation and differentiation as well as the activation of the senescence-associated secretory phenotype (SASP). In this study, we employed MHY-1685, a novel mammalian target of rapamycin (mTOR) inhibitor, and examined its long-term priming effect on the activities of senile human cardiac stem cells (hCSCs) and the functional benefits of primed hCSCs after transplantation. In vitro experiments showed that the MHY-1685?primed hCSCs exhibited higher viability in response to oxidative stress and an enhanced proliferation potential compared to that of the unprimed senile hCSCs. Interestingly, priming MHY-1685 enhanced the expression of stemness-related markers in senile hCSCs and provided the differentiation potential of hCSCs into vascular lineages. In vivo experiment with echocardiography showed that transplantation of MHY-1685?primed hCSCs improved cardiac function than that of the unprimed senile hCSCs at 4 weeks post-MI. In addition, hearts transplanted with MHY-1685-primed hCSCs exhibited significantly lower cardiac fibrosis and higher capillary density than that of the unprimed senile hCSCs. In confocal fluorescence imaging, MHY-1685?primed hCSCs survived for longer durations than that of the unprimed senile hCSCs and had a higher potential to differentiate into endothelial cells (ECs) within the infarcted hearts. These findings suggest that MHY-1685 can rejuvenate senile hCSCs by modulating autophagy and that as a senescence inhibitor, MHY-1685 can provide opportunities to improve hCSC-based myocardial regeneration.

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