Kim, Hyosuk Kim, Dongkyu Ku, Sook Hee Kim, Kwangmeyung Kim, Sun Hwa Kwon, Ick Chan 2024-01-20T01:01:26Z 2024-01-20T01:01:26Z 2021-09-05 2017-08 0920-5063 https://pubs.kist.re.kr/handle/201004/122459 Technological advances opened up new ways of directing cell fate conversion from one cell lineage to another. The direct cell conversion technique has recently attracted much attention in regenerative medicine to treat devastated organs and tissues, particularly having limited regenerative capacity such as the heart and brain. Unfortunately, its clinical application is severely limited due to a safety concern and immunogenicity of viral vectors, as human gene therapy did in the beginning stages. In this study, we examined the possibility of adopting non-viral vectors to direct cell conversion from mouse embryonic fibroblasts to induced cardiomyocytes (iCM) by transient transfection of four types of chemically synthesized microRNA mimics (miRNA-1, 133, 208, and 499). Herein, we tested several commercial and synthetic non-viral gene delivery carriers, which could be divided into three different categories: polymers [branched PEI (bPEI), bioreducible PEI (PEI-SS), deoxycholic acid-conjugated PEI (DAPEI), jetPEI T, SuperFect T], lipids (Lipofectamine 2000 T), and peptides (PepMute T). According to the analyses of physicochemical properties, cellular uptake, and cytotoxicity of the carrier/miRNA complexes, DAPEI exhibited excellent miRNA delivery efficiency to mouse embryonic fibroblasts. One week after a single treatment of DA-PEI/miRNA without other adjuvants, the cells started to express cardiomyocyte-specific markers, such as alpha-actinin and alpha-MHC, indicating the formation of cardiomyocyte-like cells. Although the overall frequency of non-viral vector induced cardiomyogenic transdifferentiation was quite low (ca. 0.2%), this study can provide compelling support to develop clinically applicable transdifferentiation techniques. English TAYLOR & FRANCIS LTD PLURIPOTENT STEM-CELLS LOW-MOLECULAR-WEIGHT GENE DELIVERY CARDIOVASCULAR DEVELOPMENT TRANSFECTION EFFICIENCY TRANSCRIPTION FACTORS DEFINED FACTORS CELLULAR UPTAKE SURFACE-CHARGE POLYETHYLENIMINE MicroRNA-mediated non-viral direct conversion of embryonic fibroblasts to cardiomyocytes: comparison of commercial and synthetic non-viral vectors Article 10.1080/09205063.2017.1287537 1 JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION, v.28, no.10-12, pp.1070 - 1085 JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION 28 10-12 1070 1085 scie scopus 000406477700016 2-s2.0-85013030292 Engineering, Biomedical Materials Science, Biomaterials Polymer Science Engineering Materials Science Polymer Science Article PLURIPOTENT STEM-CELLS LOW-MOLECULAR-WEIGHT GENE DELIVERY CARDIOVASCULAR DEVELOPMENT TRANSFECTION EFFICIENCY TRANSCRIPTION FACTORS DEFINED FACTORS CELLULAR UPTAKE SURFACE-CHARGE POLYETHYLENIMINE Non-viral delivery polyethylenimine miRNA transdifferentiation cardiomyocyte