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In vitro models of heart disease and regeneration
Author(s) -
Radisic Milica
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.459.2
Subject(s) - extracellular matrix , induced pluripotent stem cell , embryonic stem cell , in vitro , microbiology and biotechnology , myocyte , embryonic heart , stem cell , biology , chemistry , biochemistry , gene
The ability to generate human cardiomyocytes from either embryonic stem cells or induced pluripotent stem cells, provides an unprecedented opportunity to establish human in vitro models of cardiovascular disease as well as to develop replacement cardiac tissue for therapeutic applications. Here, we will present our recent efforts at generating a microarray of human cardiac microwires (CMW) using hESC derived cardiomyocytes (Hes2) and collagen gel compaction. Within this system, we recapitulated the basic microenvironment found in the heart, one which integrates cardiomyocytes, non‐myocytes, the extracellular matrix, and dynamic electromechanical forces. CMW are morphologically reproducible, maintain high cardiac protein expression in a highly dense, aligned, and suspended 3‐D extracellular matrix and can be cultured for at up to 30 days. A rapid, 7‐day maturation regimen that included electrical field stimulation yielded CMWs with a conduction velocity of 47.4 ± 12.4 cm/s, on par with healthy human heart tissue. The spontaneous beating rate in CMWs was amenable to pharmacological manipulation using lidocaine and norepinephrine while isoproterenol treatment caused hypertrophic response.