Building blocks of the human heart

Author(s):
Giacomelli, E.
Published
2019
Publication type
Doctoral Thesis

Abstract

Cardiomyocytes derived from human pluripotent stem cells

(hPSC-CMs) are arguably the best in vitro system for studying human cardiac

developmental processes and mechanisms underlying cardiac diseases. However,

hPSC-CMs are functionally immature compared to CMs in the adult heart. Additionally, the heart is organized as a complex three-dimensional (3D) organ composed of multiple cell types that are not isolated from one another but instead constantly communicate with each other to ensure proper cardiac function. By considering the heart as a collection of individual building-blocks, protocols were developed in this thesis to differentiate all of these multiple cardiac cell types from common hPSC-cardiac mesoderm progenitors and subsequently mixing them in different combinations to generate miniaturized 3D models of the heart that we termed “cardiac microtissues”.

human pluripotent stem cell differentiationhuman induced pluripotent stem cell-derived cardiomyocyteshuman induced pluripotent stem cell-derived cardiac endothelial cellshuman induced pluripotent stem cell-derived cardiac fibroblastscardiac microtissue3D cardiac tissue modelcardiomyocyte maturationcell-cell interactions
Defense date
2019-10-01
Language
English
Supervisor(s)
Mummery, C.L.
Advisor(s)
Bellin, M.; Orvola, V.V.
Committee member(s)
Goumans, M.J.T.H.; Atsma, D.E.; Passier, P.C.J.J.; Velden, J. van der; Meer, P. van der
Qualification
Ph.D.
Degree granting institution
Leiden University of Medical Center [LUMC], Leiden University, Leiden
hdl
1887/78948
ISBN(s)
9789463804288

Funding

Sponsorship
The research described in this thesis as well as its publications was supported by the following grants: European Research Council (ERCAdG 323182 STEMCARDIOVASC) and Transnational Research Project on Cardiovascular Diseases (JTC2016_FP-40-021 ACM-HF). Financial support by the Dutch Heart Foundation for the publication of this thesis is gratefully acknowledged.