title: Direct hydrogel encapsulation of pluripotent stem cells enables ontomimetic differentiation and growth of engineered human heart tissues.
abstract: Human engineered heart tissues have potential to revolutionize cardiac development research, drug-testing, and treatment of heart disease; however, implementation is limited by the need to use pre-differentiated cardiomyocytes (CMs). Here we show that by providing a 3D poly(ethylene glycol)-fibrinogen hydrogel microenvironment, we can directly differentiate human pluripotent stem cells (hPSCs) into contracting heart tissues. Our straight-forward, ontomimetic approach, imitating the process of development, requires only a single cell-handling step, provides reproducible results for a range of tested geometries and size scales, and overcomes inherent limitations in cell maintenance and maturation, while achieving high yields of CMs with developmentally appropriate temporal changes in gene expression. We demonstrate that hPSCs encapsulated within this biomimetic 3D hydrogel microenvironment develop into functional cardiac tissues composed of self-aligned CMs with evidence of ultrastructural maturation, mimicking heart development, and enabling investigation of disease mechanisms and screening of compounds on developing human heart tissue.
authors.affiliation: Department of Chemical Engineering, Auburn University, AL, USA.
authors.forename: Petra
authors.initials: P
authors.lastname: Kerscher
authors.affiliation: Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: Irene C
authors.initials: IC
authors.lastname: Turnbull
authors.affiliation: Department of Chemical Engineering, Auburn University, AL, USA.
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Hodge
authors.affiliation: Department of Chemistry and Biochemistry, Auburn University, AL, USA.
authors.forename: Joonyul
authors.initials: J
authors.lastname: Kim
authors.affiliation: Department of Biomedical Engineering, Technion-Israel Institute of Technology, Haifa, Israel.
authors.forename: Dror
authors.initials: D
authors.lastname: Seliktar
authors.affiliation: Department of Chemistry and Biochemistry, Auburn University, AL, USA.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Easley
authors.affiliation: Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: Kevin D
authors.initials: KD
authors.lastname: Costa
authors.affiliation: Department of Chemical Engineering, Auburn University, AL, USA. Electronic address: elipke@auburn.edu.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Lipke
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D018914:Cells, Immobilized / Q000166:cytology; D005786:Gene Expression Regulation / Q000187:drug effects; D006321:Heart / Q000187:drug effects* / Q000254:growth & development*; D006801:Humans; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000494:pharmacology*; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects / Q000648:ultrastructure; D039904:Pluripotent Stem Cells / Q000166:cytology* / Q000187:drug effects; D011092:Polyethylene Glycols / Q000737:chemistry; D023822:Tissue Engineering / Q000379:methods*
chemical_list: D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D011092:Polyethylene Glycols
keywords: Developing heart tissue; Embryonic; Engineered cardiac tissue; Hydrogel; Maturation; Microenvironment; PEG-fibrinogen; Pluripotent; Stem cell
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