한빛사 논문
Bong-Woo Park1,2,*, Soo-Hyun Jung1,2,*, Sanskrita Das3,*, Soon Min Lee4, Jae-Hyun Park1,2, Hyeok Kim1,2, Ji-Won Hwang1,2, Sunghun Lee5, Hyo-Jin Kim4, Hey-Yon Kim4, Seungman Jung3,6, Dong-Woo Cho7, Jinah Jang3,6,7,†, Kiwon Ban5,† and Hun-Jun Park1,2,8,†
1Department of Medical Life Science, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul 137701, Republic of Korea.
2Division of Cardiology, Department of Internal Medicine, Seoul St. Mary’s Hospital, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul 137701, Republic of Korea.
3Department of Creative IT Engineering, Pohang University of Science and Technology (POSTECH), 77 Cheongam-ro, Namgu, Pohang, Kyungbuk 37673, Republic of Korea.
4SL BIGEN Inc., 7F, Bldg. C, Korea Bio Park, Daewangpangyo-ro 700, Bundang-gu, Seongnam City, Gyeonggi-do, Republic of Korea.
5Department of Biomedical Sciences, City University of Hong Kong, Tat Chee Avenue, Kowloon, Hong Kong SAR.
6School of Interdisciplinary Bioscience and Bioengineering, POSTECH, 77 Cheongam-ro, Hyogok-dong, Nam-gu, Pohang 37673, Republic of Korea.
7Department of Mechanical Engineering, POSTECH, 77 Cheongam-ro, Hyogok-dong, Nam-gu, Pohang 37673, Republic of Korea.
8Cell Death Disease Research Center, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea.
†Corresponding author.
*These authors contributed equally to this work.
Abstract
The clinical use of human bone marrow–derived mesenchymal stem cells (BM-MSCs) has been hampered by their poor performance after transplantation into failing hearts. Here, to improve the therapeutic potential of BM-MSCs, we developed a strategy termed in vivo priming in which BM-MSCs are primed in vivo in myocardial infarction (MI)–induced hearts through genetically engineered hepatocyte growth factor–expressing MSCs (HGF-eMSCs) that are encapsulated within an epicardially implanted 3D cardiac patch. Primed BM-MSCs through HGF-eMSCs exhibited improved vasculogenic potential and cell viability, which ultimately enhanced vascular regeneration and restored cardiac function to the MI hearts. Histological analyses further demonstrated that the primed BM-MSCs survived longer within a cardiac patch and conferred cardioprotection evidenced by substantially higher numbers of viable cardiomyocytes in the MI hearts. These results provide compelling evidence that this in vivo priming strategy can be an effective means to enhance the cardiac repair of MI hearts.
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