한빛사논문
Hyosuk Kim1†, Byeong-Wook Song2†, Soon-Jung Park3, Seong Woo Choi3, Hanbyeol Moon2, Ki-Chul Hwang2, Sun-Woong Kang4, Sung-Hwan Moon2, Yoosoo Yang1, Ick Chan Kwon1,5,6*, Sun Hwa Kim1*
1Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology (KIST), Seoul 02792, Republic of Korea. 2College of Medicine, Institute for Bio-Medical Convergence, Catholic Kwandong University, Gangneung-si 25601, Republic of Korea. 3Department of Stem Cell Biology, School of Medicine, Konkuk University, Seoul 05029, Republic of Korea. 4Predictive Model Research Center, Korea Institute of Toxicology, Daejeon 34114, Republic of Korea. 5KU-KIST Graduate School of Converging Science and Technology, Korea University, Seoul 02841, Republic of Korea. 6KIST-DFCI ON-SITE-LAB, Department of Cancer Biology, Dana Farber Cancer Institute, Boston, MA 02215, USA. *Corresponding author.
†These authors contributed equally to this work.
*Corresponding author.
Abstract
Direct lineage conversion holds great promise in the regenerative medicine field for restoring damaged tissues using functionally engineered counterparts. However, current methods of direct lineage conversion, even those using virus-mediated transgenic expression of tumorigenic factors, are extremely inefficient (~25%). Thus, advanced methodologies capable of revolutionizing efficiency and addressing safety concerns are key to clinical translation of these technologies. Here, we propose an extracellular vesicle (EV)–guided, nonviral, direct lineage conversion strategy to enhance transdifferentiation of fibroblasts to induced cardiomyocyte-like cells (iCMs). The resulting iCMs have typical cardiac Ca2+ transients and electrophysiological features and exhibit global gene expression profiles similar to those of cardiomyocytes. This is the first demonstration of the use of EVs derived from embryonic stem cells undergoing cardiac differentiation as biomimetic tools to induce cardiac reprogramming with extremely high efficiency (>60%), establishing a general, more readily accessible platform for generating a variety of specialized somatic cells through direct lineage conversion.
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