한빛사 논문
Hyeok Kim1,2,12, Soon-Jung Park3,12, Jae-Hyun Park1,4,12, Sunghun Lee4, Bong-Woo Park1,2, Soon Min Lee5, Ji-Won Hwang1,2, Jin-Ju Kim1,2, Byeongmin Kang6, Woo-Sup Sim1,2, Hyo-Jin Kim5, Seung Hwan Jeon7, Dong-Bin Kim8, Jinah Jang6, Dong-Woo Cho9, Sung-Hwan Moon3,10,*, Hun-Jun Park1,2,11,* and Kiwon Ban4,*
1Department of Biomedicine & Health Sciences, College of Medicine, The Catholic University of Korea, Seoul, South Korea. 2Division of Cardiology, Department of Internal Medicine, Seoul St. Mary’s Hospital, The Catholic University of Korea, Seoul, South Korea. 3Research Institute, T&R Biofab Co., Ltd., Siheung, South Korea. 4Department of Biomedical Sciences, City University of Hong Kong, Kowloon Tong, Hong Kong. 5SL BIGEN, Inc., Seongnam, South Korea. 6Department of Creative IT Engineering and School of Interdisciplinary Bioscience and Bioengineering, Pohang University of Science and Technology, Pohang, South Korea. 7Department of Urology, College of Medicine, The Catholic University of Korea, Seoul, South Korea. 8Division of Cardiology, Department of Internal Medicine, The Catholic University of Korea, Seoul, South Korea. 9Department of Mechanical Engineering, Pohang University of Science and Technology, Pohang, South Korea. 10Department of Animal Biotechnology, Sangji University, Wonju, South Korea. 11Cell Death Disease Research Center, College of Medicine, The Catholic University of Korea, Seoul, South Korea. 12These authors contributed equally: Hyeok Kim, Soon-Jung Park, Jae-Hyun Park.
*Corresponding author.
Abstract
Since an impaired coronary blood supply following myocardial infarction (MI) negatively affects heart function, therapeutic neovascularization is considered one of the major therapeutic strategies for cell-based cardiac repair. Here, to more effectively achieve therapeutic neovascularization in ischemic hearts, we developed a dual stem cell approach for effective vascular regeneration by utilizing two distinct types of stem cells, CD31+-endothelial cells derived from human induced pluripotent stem cells (hiPSC-ECs) and engineered human mesenchymal stem cells that continuously secrete stromal derived factor-1α (SDF-eMSCs), to simultaneously promote natal vasculogenesis and angiogenesis, two core mechanisms of neovascularization. To induce more comprehensive vascular regeneration, we intramyocardially injected hiPSC-ECs to produce de novo vessels, possibly via vasculogenesis, and a 3D cardiac patch encapsulating SDF-eMSCs (SDF-eMSC-PA) to enhance angiogenesis through prolonged secretion of paracrine factors, including SDF-1α, was implanted into the epicardium of ischemic hearts. We verified that hiPSC-ECs directly contribute to de novo vessel formation in ischemic hearts, resulting in enhanced cardiac function. In addition, the concomitant implantation of SDF1α-eMSC-PAs substantially improved the survival, retention, and vasculogenic potential of hiPSC-ECs, ultimately achieving more comprehensive neovascularization in the MI hearts. Of note, the newly formed vessels through the dual stem cell approach were significantly larger and more functional than those formed by hiPSC-ECs alone. In conclusion, these results provide compelling evidence that our strategy for effective vascular regeneration can be an effective means to treat ischemic heart disease.
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