TY - JOUR
T1 - A New Versatile Platform for Assessment of Improved Cardiac Performance in Human-Engineered Heart Tissues
AU - Ribeiro, Marcelo C.
AU - Rivera-Arbelaez, Jose M.
AU - Cofino-Fabres, Carla
AU - Schwach, Verena
AU - Slaats, Rolf H.
AU - ten Den, Simone A.
AU - Vermeul, Kim
AU - van den Berg, Albert
AU - Perez-Pomares, Jose M.
AU - Segerink, Loes I.
AU - Guadix, Juan A.
AU - Passier, Robert
N1 - Funding Information:
This work was supported by the Netherlands Organ-on-Chip Initiative, an NWO Gravitation project (024.003.001) funded by the Ministry of Education, Culture, and Science of the government of the Netherlands; (Health Holland, LSHM19004); the TOP-ZonMw grant; (ZonMw, TOP-00812-98-17061); ERA-CVD 2016T092; the Dutch Heart Foundation; the Consejer?a de Salud, Junta de Andaluc?a (grant PIER-0084-2019); and the Spanish Ministerio de Ciencia, Innovaci?n y Universidades (grants RTI2018-095410-BI00 and RD16/0011/0030).
Funding Information:
Funding: This work was supported by the Netherlands Organ-on-Chip Initiative, an NWO Gravitation project (024.003.001) funded by the Ministry of Education, Culture, and Science of the government of the Netherlands; (Health Holland, LSHM19004); the TOP-ZonMw grant; (ZonMw, TOP-00812-98-17061); ERA-CVD 2016T092; the Dutch Heart Foundation; the Consejería de Salud, Junta de Andalucía (grant PIER-0084-2019); and the Spanish Ministerio de Ciencia, Innovación y Univer-sidades (grants RTI2018-095410-BI00 and RD16/0011/0030).
Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2022/2/4
Y1 - 2022/2/4
N2 - Cardiomyocytes derived from human pluripotent stem cells (hPSC-CMs) hold a great potential as human in vitro models for studying heart disease and for drug safety screening. Nevertheless, their associated immaturity relative to the adult myocardium limits their utility in cardiac research. In this study, we describe the development of a platform for generating three-dimensional engineered heart tissues (EHTs) from hPSC-CMs for the measurement of force while under mechanical and electrical stimulation. The modular and versatile EHT platform presented here allows for the formation of three tissues per well in a 12-well plate format, resulting in 36 tissues per plate. We compared the functional performance of EHTs and their histology in three different media and demonstrated that tissues cultured and maintained in maturation medium, containing triiodothyronine (T3), dexamethasone, and insulin-like growth factor-1 (TDI), resulted in a higher force of contraction, sarcomeric organization and alignment, and a higher and lower inotropic response to isoproterenol and nifedipine, respectively. Moreover, in this study, we highlight the importance of integrating a serum-free maturation medium in the EHT platform, making it a suitable tool for cardiovascular research, disease modeling, and preclinical drug testing
AB - Cardiomyocytes derived from human pluripotent stem cells (hPSC-CMs) hold a great potential as human in vitro models for studying heart disease and for drug safety screening. Nevertheless, their associated immaturity relative to the adult myocardium limits their utility in cardiac research. In this study, we describe the development of a platform for generating three-dimensional engineered heart tissues (EHTs) from hPSC-CMs for the measurement of force while under mechanical and electrical stimulation. The modular and versatile EHT platform presented here allows for the formation of three tissues per well in a 12-well plate format, resulting in 36 tissues per plate. We compared the functional performance of EHTs and their histology in three different media and demonstrated that tissues cultured and maintained in maturation medium, containing triiodothyronine (T3), dexamethasone, and insulin-like growth factor-1 (TDI), resulted in a higher force of contraction, sarcomeric organization and alignment, and a higher and lower inotropic response to isoproterenol and nifedipine, respectively. Moreover, in this study, we highlight the importance of integrating a serum-free maturation medium in the EHT platform, making it a suitable tool for cardiovascular research, disease modeling, and preclinical drug testing
KW - Versatile platform
KW - Engineered heart tissues
KW - Serum-free
KW - Contractile force
KW - Cardiac performance
KW - hPSC-CMs
U2 - 10.3390/jpm12020214
DO - 10.3390/jpm12020214
M3 - Article
SN - 2075-4426
VL - 12
JO - Journal of Personalized Medicine
JF - Journal of Personalized Medicine
IS - 2
M1 - 214
ER -
