Bong-Woo Park^1,2,*, Soo-Hyun Jung^1,2,*, Sanskrita Das^3,*, Soon Min Lee⁴, Jae-Hyun Park^1,2, Hyeok Kim^1,2, Ji-Won Hwang^1,2, Sunghun Lee⁵, Hyo-Jin Kim⁴, Hey-Yon Kim⁴, Seungman Jung^3,6, Dong-Woo Cho⁷, Jinah Jang^3,6,7,†, Kiwon Ban^5,† and Hun-Jun Park^1,2,8,†

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.

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.