title: Cardiomyocytes derived from human embryonic and induced pluripotent stem cells: comparative ultrastructure.
abstract: Induced pluripotent stem cells (iPSC) are generated from fully differentiated somatic cells that were reprogrammed into a pluripotent state. Human iPSC which can be obtained from various types of somatic cells such as fibroblasts or keratinocytes can differentiate into cardiomyocytes (iPSC-CM), which exhibit cardiac-like transmembrane action potentials, intracellular Ca(2+) transients and contractions. While major features of the excitation-contraction coupling of iPSC-CM have been well-described, very little is known on the ultrastructure of these cardiomyocytes. The ultrastructural features of 31-day-old (post-plating) iPSC-CM generated from human hair follicle keratinocytes (HFKT-iPSC-CM) were analysed by electron microscopy, and compared with those of human embryonic stem-cell-derived cardiomyocytes (hESC-CM). The comparison showed that cardiomyocytes from the two sources share similar proprieties. Specifically, HFKT-iPSC-CM and hESC-CM, displayed ultrastructural features of early and immature phenotype: myofibrils with sarcomeric pattern, large glycogen deposits, lipid droplets, long and slender mitochondria, free ribosomes, rough endoplasmic reticulum, sarcoplasmic reticulum and caveolae. Noteworthy, the SR is less developed in HFKT-iPSC-CM. We also found in both cell types: (1) 'Ca(2+)-release units', which connect the peripheral sarcoplasmic reticulum with plasmalemma; and (2) intercellular junctions, which mimic intercalated disks (desmosomes and fascia adherens). In conclusion, iPSC and hESC differentiate into cardiomyocytes of comparable ultrastructure, thus supporting the notion that iPSC offer a viable option for an autologous cell source for cardiac regenerative therapy.
authors: Victor Babeş National Institute of Pathology, Bucharest, Romania.
authors: Mihaela
authors: M
authors: Gherghiceanu
authors: Lili
authors: L
authors: Barad
authors: Atara
authors: A
authors: Novak
authors: Irina
authors: I
authors: Reiter
authors: Joseph
authors: J
authors: Itskovitz-Eldor
authors: Ofer
authors: O
authors: Binah
authors: L M
authors: LM
authors: Popescu
mesh_terms: D002118:Calcium / Q000378:metabolism; D021941:Caveolae / Q000648:ultrastructure; D002454:Cell Differentiation; D002478:Cells, Cultured; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000502:physiology; D004721:Endoplasmic Reticulum / Q000648:ultrastructure; D056966:Excitation Contraction Coupling; D005347:Fibroblasts / Q000166:cytology; D018859:Hair Follicle / Q000378:metabolism; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000502:physiology; D015603:Keratinocytes / Q000166:cytology; D008564:Membrane Potentials; D008854:Microscopy, Electron; D008929:Mitochondria, Heart / Q000648:ultrastructure; D009200:Myocardial Contraction; D032383:Myocytes, Cardiac / Q000648:ultrastructure*; D012519:Sarcoplasmic Reticulum / Q000648:ultrastructure
chemical_list: D002118:Calcium