title: Making human cardiomyocytes up to date: Derivation, maturation state and perspectives.
abstract: In vitro generation of cardiomyocytes (CMs) from human cells opens the possibility to develop patient-specific therapies to various cardiomyopathies. By establishing the in vitro reprograming methods that produce human CMs, we learn about what is involved in the development of specific CM subtypes. In this review, we summarize the latest achievements in CM generation technologies, emphasizing the differentiation methods of specific CM subtypes. We also relate the biological properties and functions of the in vitro-generated CMs to those of their in vivo counterparts. Furthermore, we describe the main problem of current CM derivation methods - maturation of CMs. We subsequently discuss biochemical and physical stimuli that are used to overcome the maturation problems of in vitro-derived CMs. As a result, a more holistic approach with controllable environment and timing of specific stimuli for creation of more mature engineered heart tissues is described as well. Finally, we propose a novel approach in which enhancing energy transfer mechanisms in the immature CMs might help to overcome the current hurdle of incomplete in vitro differentiation.
authors.affiliation: Institute of Pharmacology and Toxicology, Technische Universität Dresden, Fetscherstr. 74, 01307 Dresden, Germany.
authors.forename: Tomasz J
authors.initials: TJ
authors.lastname: Kolanowski
authors.affiliation: Institute of Pharmacology and Toxicology, Technische Universität Dresden, Fetscherstr. 74, 01307 Dresden, Germany; School of Life Science and Technology, ShanghaiTech University, 100 Haike Rd., 201210 Shanghai, China.
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Antos
authors.affiliation: Institute of Pharmacology and Toxicology, Technische Universität Dresden, Fetscherstr. 74, 01307 Dresden, Germany. Electronic address: kaomei.guan@tu-dresden.de.
authors.forename: Kaomei
authors.initials: K
authors.lastname: Guan
mesh_terms: D000200:Action Potentials / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000502:physiology*; D032383:Myocytes, Cardiac / Q000502:physiology*
keywords: Cardiomyocyte derivation protocols; Cardiomyocyte maturation; In vitro derived-cardiomyocyte applications; Induced pluripotent stem cells; Stem cells