제1저자 이지윤(BK21 졸업) 이시형(가톨릭관동대)
교신저자 임소연 황기철(가톨릭관동대)
Stem Cell Res Ther. 2017 Sep 19ɖ(1):195. doi: 10.1186/s13287-017-0647-6.
Adipose-derived stem cell-released osteoprotegerin protects cardiomyocytes from reactive oxygen species-induced cell death.
Lee J1, Lee S2, Lee CY3, Seo HH1, Shin S3, Choi JW2,4, Kim SW2, Park JC1,5, Lim S6, Hwang KC7.
1Brain Korea 21 PLUS Project for Medical Science, Yonsei University, Seoul, Korea.2Institute for Bio-Medical Convergence, College of Medicine, Catholic Kwandong University, Gangneung, Gangwon-do, Korea.3Department of Integrated Omics for Biomedical Sciences, Yonsei University, Seoul, South Korea.4Department of Environmental Engineering, Catholic Kwandong University, Gangneung-si, Gangwon-do, Republic of Korea.5Cellbiocontrol Laboratory, Department of Medical Engineering, Yonsei University College of Medicine, Seoul, Republic of Korea.6Institute for Bio-Medical Convergence, College of Medicine, Catholic Kwandong University, Gangneung, Gangwon-do, Korea. firstname.lastname@example.orgInstitute for Bio-Medical Convergence, College of Medicine, Catholic Kwandong University, Gangneung, Gangwon-do, Korea. email@example.com.
The paracrine effect is likely the major mechanism of the adipose-derived stem cell (ASC)-mediated cardioprotective effect. However, the exact composition and nature of ASC-released paracrine factors remain elusive. In the present study, we examined the effect of osteoprotegerin (OPG), a stem cell-released decoy receptor for death ligand, on the survival of cardiomyocytes exposed to oxidative stress.
The production of OPG from ASCs under oxidative stress was determined by ELISA and immunohistochemistry. The effects of OPG and the OPG-containing conditioned media of ASCs on the survival of cardiomyocytes were determined using a cell viability assay.
Hydrogen peroxide (H2O2) significantly increased OPG production from ASCs in vitro, and OPG production from the ASCs transplanted into the ischemia-reperfusion-injured heart was also observed. OPG significantly attenuated cardiomyocyte death in vitro. OPG-containing conditioned media of ASCs also significantly protected cardiomyocytes. Delivery of siRNA specific to OPG significantly decreased the OPG production of ASCs, and also offset the protective effect of the conditioned media of ASCs.
Our study strongly suggests that OPG is one of the prosurvival factors released from ASCs that may contribute to the ASC-mediated cardioprotection and calls for further studies to elucidate detailed underlying mechanisms.