Year: 2018
Type: article
Abstract: Induced pluripotent stem cells (iPSCs) hold great promise for regenerative medicine; however, their potential clinical application is hampered by the low efficiency of somatic cell reprogramming. Here, we show that the synergistic activity of synthetic modified mRNAs encoding reprogramming factors and miRNA-367/302s delivered as mature miRNA mimics greatly enhances the reprogramming of human primary fibroblasts into iPSCs. This synergistic activity is dependent upon an optimal RNA transfection regimen and culturing conditions tailored specifically to human primary fibroblasts. As a result, we can now generate up to 4,019 iPSC colonies from only 500 starting human primary neonatal fibroblasts and reprogram up to 90.7% of individually plated cells, producing multiple sister colonies. This methodology consistently generates clinically relevant, integration-free iPSCs from a variety of human patient's fibroblasts under feeder-free conditions and can be applicable for the clinical translation of iPSCs and studying the biology of reprogramming.
Source: Nature Communications
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $6,990
Funders: U.S. Department of Defense, Foundation for Ichthyosis and Related Skin Types, Dystrophic Epidermolysis Bullosa Research Association, Koning Boudewijnstichting, National Institutes of Health, Cancer Center, University of Colorado, National Cancer Institute, National Institute of Allergy and Infectious Diseases, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Center for Advancing Translational Sciences, Linda Crnic Institute for Down Syndrome, University of Colorado School of Medicine, Anschutz Medical Campus
Awards: G1309041795, G1368206816, G1565180698, G4119534169, Molecular Analysis, Modeling and Correction of Skin Diseases Core Center, Autoimmunity risk alleles compromising B cell anergy, G5324093878, G5850682332, Colorado Clinical and Translational Sciences Institute, Testing the Therapeutic Potential of iPS Cells for Inherited Skin Diseases, Training in Translational Research of Skin Diseases, University of Colorado Cancer Center Support Grant
OpenAlex ID: W2791520226