Early first trimester human embryonic cardiac Islet-1 progenitor cells and cardiomyocytes: Immunohistochemical and electrophysiological characterization.
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.
Genead
Rami
R
Karolinska Institute at Clinical Research Centre, Novum, Sweden.
Danielsson
Christian
C
Wärdell
Eva
E
Kjaeldgaard
Anders
A
Westgren
Magnus
M
Sundström
Erik
E
Franco-Cereceda
Anders
A
Sylvén
Christer
C
Grinnemo
Karl-Henrik
KH
D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D003584:Cytological Techniques; D005260:Female; D006321:Heart / Q000196:embryology*; D018398:Homeodomain Proteins / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D060850:LIM-Homeodomain Proteins; D046529:Microscopy, Electron, Transmission; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism*; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D014157:Transcription Factors
D018398:Homeodomain Proteins; D060850:LIM-Homeodomain Proteins; D014157:Transcription Factors; C063843:insulin gene enhancer binding protein Isl-1