title: Induced myogenic commitment of human chondrocytes via non-viral delivery of minicircle DNA.
abstract: Lineage conversion from one somatic cell type to another is an attractive approach for deriving specific therapeutic cell generation. In order to bypass inducing pluripotent stage, transdifferentiation/direct conversion technologies have been recently developed. We report the development of a direct conversion methodology in which cells are transdifferentiated through a plastic intermediate state induced by exposure to non-integrative minicircle DNA (MCDNA)-based reprogramming factors, followed by differentiation into myoblasts. In order to increase the MCDNA delivery efficiency, reprogramming factors were delivered into the chondrocytes via electroporation followed by poly (β-amino esters) (PBAE) transfection. We used this approach to convert human chondrocytes to myoblast, and with treatment of SB-431542, an inhibitor of the activin receptor-like kinase receptors, to enhance myogenic commitment. Differentiated cells exhibited expression of myogenic markers such as MyoD and Myog. This methodology for direct lineage conversion from chondrocytes to myoblast represents a novel non-viral Method to convert hard-to-transfect cells to other lineage.
authors.affiliation: School of Chemical and Biological Engineering, BioMAX Institute, Seoul National University, Seoul, Republic of Korea.
authors.forename: Jieun
authors.initials: J
authors.lastname: Hong
authors.affiliation: School of Chemical and Biological Engineering, BioMAX Institute, Seoul National University, Seoul, Republic of Korea.
authors.forename: Eunjee A
authors.initials: EA
authors.lastname: Lee
authors.affiliation: School of Chemical and Biological Engineering, BioMAX Institute, Seoul National University, Seoul, Republic of Korea.
authors.forename: Eun-Seo
authors.initials: ES
authors.lastname: Lee
authors.affiliation: School of Chemical and Biological Engineering, BioMAX Institute, Seoul National University, Seoul, Republic of Korea.
authors.forename: Giyoung
authors.initials: G
authors.lastname: Jung
authors.affiliation: College of Pharmacy, Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul, Republic of Korea.
authors.forename: Hansaem
authors.initials: H
authors.lastname: Jeong
authors.affiliation: Cellular and Molecular Medicine Graduate Program, Johns Hopkins School of Medicine, Baltimore, MD, USA.
authors.forename: Hwajin
authors.initials: H
authors.lastname: Lee
authors.affiliation: College of Pharmacy, Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul, Republic of Korea. Electronic address: hyukjin@ewha.ac.kr.
authors.forename: Hyukjin
authors.initials: H
authors.lastname: Lee
authors.affiliation: School of Chemical and Biological Engineering, BioMAX Institute, Seoul National University, Seoul, Republic of Korea. Electronic address: nshwang@snu.ac.kr.
authors.forename: Nathaniel S
authors.initials: NS
authors.lastname: Hwang
mesh_terms: D000273:Adipose Tissue / Q000166:cytology; D001549:Benzamides / Q000494:pharmacology; D054338:Cell Transdifferentiation; D002478:Cells, Cultured; D065150:Cellular Reprogramming; D019902:Chondrocytes / Q000166:cytology*; D004247:DNA / Q000008:administration & dosage*; D004149:Dioxoles / Q000494:pharmacology; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology; D032446:Myoblasts / Q000166:cytology*; D014162:Transfection
chemical_list: C459179:4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide; D001549:Benzamides; D004149:Dioxoles; D004247:DNA
keywords: Chondrocyte; Minicircle DNA; Nanoparticle; Non-viral delivery; Transdifferentiation; Transfection