Journal of Controlled Release 2015-02-28

Induced myogenic commitment of human chondrocytes via non-viral delivery of minicircle DNA.

Jieun Hong, Eunjee A Lee, Eun-Seo Lee, Giyoung Jung, Hansaem Jeong, Hwajin Lee, Hyukjin Lee, Nathaniel S Hwang

Index: J. Control. Release 200 , 212-21, (2015)

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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. Copyright © 2015 Elsevier B.V. All rights reserved.