title: Effective cardiac myocyte differentiation of human induced pluripotent stem cells requires VEGF.
abstract: Perhaps one of the most significant achievements in modern science is the discovery of human induced pluripotent stem cells (hiPSCs), which have paved the way for regeneration therapy using patients' own cells. Cardiomyocytes differentiated from hiPSCs (hiPSC-CMs) could be used for modelling patients with heart failure, for testing new drugs, and for cellular therapy in the future. However, the present cardiomyocyte differentiation protocols exhibit variable differentiation efficiency across different hiPSC lines, which inhibit the application of this technology significantly. Here, we demonstrate a novel myocyte differentiation protocol that can yield a significant, high percentage of cardiac myocyte differentiation (>85%) in 2 hiPSC lines, which makes the fabrication of a human cardiac muscle patch possible. The established hiPSCs cell lines being examined include the transgene integrated UCBiPS7 derived from cord blood cells and non-integrated PCBC16iPS from skin fibroblasts. The results indicate that hiPSC-CMs derived from established hiPSC lines respond to adrenergic or acetylcholine stimulation and beat regularly for greater than 60 days. This data also demonstrates that this novel differentiation protocol can efficiently generate hiPSC-CMs from iPSC lines that are derived not only from fibroblasts, but also from blood mononuclear cells.
authors: Division of Cardiology, Department of Medicine, University of Minnesota Medical School, Minneapolis, Minnesota, United States of America.
authors: Lei
authors: L
authors: Ye
authors: Sophia
authors: S
authors: Zhang
authors: Lucas
authors: L
authors: Greder
authors: James
authors: J
authors: Dutton
authors: Susan A
authors: SA
authors: Keirstead
authors: Mike
authors: M
authors: Lepley
authors: Liying
authors: L
authors: Zhang
authors: Dan
authors: D
authors: Kaufman
authors: Jianyi
authors: J
authors: Zhang
mesh_terms: D028341:Activins / Q000494:pharmacology; D000818:Animals; D055415:Bone Morphogenetic Protein 4 / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D002460:Cell Line; D019070:Cell Lineage / Q000187:drug effects; D018920:Coculture Techniques; D005312:Fetal Blood / Q000166:cytology / Q000187:drug effects; D005347:Fibroblasts / Q000166:cytology; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000378:metabolism; D051379:Mice; D009206:Myocardium / Q000166:cytology*; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism / Q000494:pharmacology
chemical_list: C525809:BMP4 protein, human; D055415:Bone Morphogenetic Protein 4; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C422405:activin A; D028341:Activins