TGF-beta1 induces efficient differentiation of human cardiomyocyte progenitor cells into functional cardiomyocytes in vitro.
The adult mammalian heart has limited regenerative capacity and was generally considered to contain no dividing cells. Recently, however, a resident population of progenitor cells has been identified, which could represent a new source of cardiomyocytes. Here, we describe the efficient isolation and propagation of human cardiomyocyte progenitor cells (hCMPCs) from fetal heart and patient biopsies. Establishment of hCMPC cultures was remarkably reproducible, with over 70% of adult atrial biopsies resulting in robustly expanding cell populations. Following the addition of transforming growth factor beta, almost all cells differentiated into spontaneously beating myocytes with characteristic cross striations. hCMPC-derived cardiomyocytes showed gap-junctional communication and action potentials of maturing cardiomyocytes. These are the first cells isolated from human heart that proliferate and form functional cardiomyocytes without requiring coculture with neonatal myocytes. Their scalability and homogeneity are unique and provide an excellent basis for developing physiological, pharmacological, and toxicological assays on human heart cells in vitro.
Goumans
Marie-José
MJ
Laboratory of Experimental Cardiology, Department of Cardiology, Division of Heart and Lung, University Medical Center, Heidelberglaan 100, Utrecht, The Netherlands.
de Boer
Teun P
TP
Smits
Anke M
AM
van Laake
Linda W
LW
van Vliet
Patrick
P
Metz
Corina H G
CH
Korfage
Tom H
TH
Kats
K Peter
KP
Hochstenbach
Ron
R
Pasterkamp
Gerard
G
Verhaar
Marianne C
MC
van der Heyden
Marcel A G
MA
de Kleijn
Dominique
D
Mummery
Christine L
CL
van Veen
Toon A B
TA
Sluijter
Joost P G
JP
Doevendans
Pieter A
PA
D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000187:drug effects*; D049109:Cell Proliferation; D002469:Cell Separation; D006801:Humans; D032383:Myocytes, Cardiac / Q000166:cytology*; D013234:Stem Cells / Q000166:cytology*; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*
D053773:Transforming Growth Factor beta1