Early first trimester human embryonic cardiac Islet-1 progenitor cells and cardiomyocytes: Immunohistochemical and electrophysiological characterization |
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Authors: | Rami Genead Christian Danielsson Eva Wärdell Anders Kjaeldgaard Magnus Westgren Erik Sundström Anders Franco-Cereceda Christer Sylvén Karl-Henrik Grinnemo |
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Affiliation: | 1. Karolinska Institute at Clinical Research Centre, Novum, and Department of Medicine, Division of Cardiology, Karolinska University Hospital, Stockholm, Sweden;2. Karolinska Institute at Clinical Research Centre, Novum, and Centre for Fetal Medicine, Karolinska University Hospital, Stockholm, Sweden;3. Karolinska Institute at Clinical Research Centre, Novum, and Department of Neurobiology, Care Sciences and Society, Division of Neurodegeneration, Karolinska University Hospital, Stockholm, Sweden;4. Karolinska Institute at Clinical Research Centre, Novum, and Department of Molecular Medicine and Surgery, Division of Cardiothoracic Surgery and Anaesthesiology, Karolinska University Hospital, S-171 76, Stockholm, Sweden |
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Abstract: | The aims of this study were to systematically characterize the distribution, proliferation, and differentiation of Islet-1+(Isl1+) progenitor cells in the early first trimester human embryonic heart during which period most of the organogenesis takes place. In hearts of gestational week 5 to 10 Isl1+cells were identified and mainly clustered in the outflow tract and to a lesser extent in the atria and in the right ventricle. Some of the clusters were also troponin T+. Unexpectedly a only few Isl1+cells were Ki67+while in the ventricles a majority of Isl1?troponinT+cells were Ki67+. Cultures derived from the digested embryonic heart developed into spontaneously beating cardiospheres. At harvest cells in these cardiospheres showed frequent expression of troponin T+and Nkx2.5+, while Isl1 was expressed only in scattered cells. Only a minority of the cultured cells expressed Ki67. The cardiospheres could be frozen, thawed, and recultured to beating cardiospheres. In a multielectrode array system, the beating cardiospheres were responsive to adrenergic stimulation and exhibited rate-dependent action potential duration. In conclusion, the early first trimester human embryonic heart expresses clusters of Isl1+cells, some of which differentiate into cardiomyocytes. Unexpectedly, only a minority of the Isl1+cells, while a majority of ventricular cardiomyocytes, were proliferating. Spontaneously beating cardiospheres could be derived from the human embryonic heart and these cardiospheres showed functional frequency control. |
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