title: Heparin Promotes Cardiac Differentiation of Human Pluripotent Stem Cells in Chemically Defined Albumin-Free Medium, Enabling Consistent Manufacture of Cardiomyocytes.
abstract: Cardiomyocytes can be differentiated from human pluripotent stem cells (hPSCs) in defined conditions, but efficient and consistent cardiomyocyte differentiation often requires expensive reagents such as B27 supplement or recombinant albumin. Using a chemically defined albumin-free (E8 basal) medium, we identified heparin as a novel factor that significantly promotes cardiomyocyte differentiation efficiency, and developed an efficient method to differentiate hPSCs into cardiomyocytes. The treatment with heparin helped cardiomyocyte differentiation consistently reach at least 80% purity (up to 95%) from more than 10 different hPSC lines in chemically defined Dulbecco's modified Eagle's medium/F-12-based medium on either Matrigel or defined matrices like vitronectin and Synthemax. One of heparin's main functions was to act as a Wnt modulator that helped promote robust and consistent cardiomyocyte production. Our study provides an efficient, reliable, and cost-effective method for cardiomyocyte derivation from hPSCs that can be used for potential large-scale drug screening, disease modeling, and future cellular therapies. Stem Cells Translational Medicine 2017;6:527-538.
authors.affiliation: National Heart, Lung and Blood Institute, NIH, Bethesda, Maryland, USA.
authors.forename: Yongshun
authors.initials: Y
authors.lastname: Lin
authors.affiliation: National Heart, Lung and Blood Institute, NIH, Bethesda, Maryland, USA.
authors.forename: Kaari L
authors.initials: KL
authors.lastname: Linask
authors.affiliation: NIH Stem Cell Unit, NIH, Bethesda, Maryland, USA.
authors.forename: Barbara
authors.initials: B
authors.lastname: Mallon
authors.affiliation: National Institute of Neurological Disorders and Stroke, NIH, Bethesda, Maryland, USA.
authors.forename: Kory
authors.initials: K
authors.lastname: Johnson
authors.affiliation: Uniformed Services University of Health Sciences, Bethesda, Maryland, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Klein
authors.affiliation: National Heart, Lung and Blood Institute, NIH, Bethesda, Maryland, USA.
authors.forename: Jeanette
authors.initials: J
authors.lastname: Beers
authors.affiliation: National Heart, Lung and Blood Institute, NIH, Bethesda, Maryland, USA.
authors.forename: Wen
authors.initials: W
authors.lastname: Xie
authors.affiliation: National Heart, Lung and Blood Institute, NIH, Bethesda, Maryland, USA.
authors.forename: Yubin
authors.initials: Y
authors.lastname: Du
authors.affiliation: National Heart, Lung and Blood Institute, NIH, Bethesda, Maryland, USA.
authors.forename: Chengyu
authors.initials: C
authors.lastname: Liu
authors.affiliation: Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
authors.forename: Yinzhi
authors.initials: Y
authors.lastname: Lai
authors.affiliation: National Heart, Lung and Blood Institute, NIH, Bethesda, Maryland, USA.|Center for Regenerative Medicine, NIH, Bethesda, Maryland, USA.
authors.forename: Jizhong
authors.initials: J
authors.lastname: Zou
authors.affiliation: Uniformed Services University of Health Sciences, Bethesda, Maryland, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Haigney
authors.affiliation: Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
authors.forename: Hushan
authors.initials: H
authors.lastname: Yang
authors.affiliation: Center for Regenerative Medicine, NIH, Bethesda, Maryland, USA.
authors.forename: Mahendra
authors.initials: M
authors.lastname: Rao
authors.affiliation: National Heart, Lung and Blood Institute, NIH, Bethesda, Maryland, USA.|Faculty of Health Sciences, University of Macau, Tapai, Macau, People's Republic of China.
authors.forename: Guokai
authors.initials: G
authors.lastname: Chen
mesh_terms: D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects*; D003470:Culture Media / Q000737:chemistry*; D006493:Heparin / Q000494:pharmacology*; D000066449:Human Embryonic Stem Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000187:drug effects* / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism; D010641:Phenotype; D013997:Time Factors; D060449:Wnt Signaling Pathway / Q000187:drug effects
chemical_list: D003470:Culture Media; D006493:Heparin
keywords: Cardiac; Cell culture; Embryonic stem cells; Heparin; Induced pluripotent stem cells