Effective Cardiac Myocyte Differentiation of Human Induced Pluripotent Stem Cells Requires VEGF
Open Access
- 10 January 2013
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 8 (1), e53764
- https://doi.org/10.1371/journal.pone.0053764
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.Keywords
This publication has 35 references indexed in Scilit:
- Bioenergetic and Functional Consequences of Cellular TherapyCirculation Research, 2012
- Robust cardiomyocyte differentiation from human pluripotent stem cells via temporal modulation of canonical Wnt signalingProceedings of the National Academy of Sciences of the United States of America, 2012
- Cardiac stem cells in patients with ischaemic cardiomyopathy (SCIPIO): initial results of a randomised phase 1 trialThe Lancet, 2011
- Epigenetic memory in induced pluripotent stem cellsNature, 2010
- Intracoronary Administration of Cardiac Progenitor Cells Alleviates Left Ventricular Dysfunction in Rats With a 30-Day-Old InfarctionCirculation, 2010
- Induced Pluripotent Stem Cell Lines Derived from Human Somatic CellsScience, 2007
- Induction of Pluripotent Stem Cells from Adult Human Fibroblasts by Defined FactorsCell, 2007
- Characterization of human embryonic stem cell lines by the International Stem Cell InitiativeNature Biotechnology, 2007
- Generation of germline-competent induced pluripotent stem cellsNature, 2007
- Induction of Pluripotent Stem Cells from Mouse Embryonic and Adult Fibroblast Cultures by Defined FactorsCell, 2006