Oxygen Is an Ambivalent Factor for the Differentiation of Human
Pluripotent Stem Cells in Cardiac 2D Monolayer and 3D Cardiac
Spheroids

J 2021

Oxygen Is an Ambivalent Factor for the Differentiation of Human Pluripotent Stem Cells in Cardiac 2D Monolayer and 3D Cardiac Spheroids

SOUIDI, M., Y. SLEIMAN, Ivana AĆIMOVIĆ, Jan PŘIBYL, A. CHARRABI et. al.

Basic information

Original name

Oxygen Is an Ambivalent Factor for the Differentiation of Human Pluripotent Stem Cells in Cardiac 2D Monolayer and 3D Cardiac Spheroids

Authors

SOUIDI, M., Y. SLEIMAN, Ivana AĆIMOVIĆ (688 Serbia, belonging to the institution), Jan PŘIBYL (203 Czech Republic, belonging to the institution), A. CHARRABI, V. BAECKER, V. SCHEUERMANN, Martin PEŠL (203 Czech Republic, guarantor, belonging to the institution), Šárka JELÍNKOVÁ (203 Czech Republic, belonging to the institution), Petr SKLÁDAL (203 Czech Republic, belonging to the institution), Petr DVOŘÁK (203 Czech Republic, belonging to the institution), A. LACAMPAGNE, Vladimír ROTREKL (203 Czech Republic, belonging to the institution) and A. C. MELI

Edition

International Journal of Molecular Sciences, Basel, Multidisciplinary Digital Publishing Institute, 2021, 1422-0067

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10608 Biochemistry and molecular biology

Country of publisher

Switzerland

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 6.208

RIV identification code

RIV/00216224:14740/21:00120132

Organization unit

Central European Institute of Technology

DOI

http://dx.doi.org/10.3390/ijms22020662

UT WoS

000611336200001

Keywords in English

hPSC-derived cardiomyocytes; cardiac spheroids; embryoid bodies; 2D-monolayer; oxygen exposure; intracellular calcium handling; mitochondrial oxygen consumption; contractile properties

Abstract

V originále

Numerous protocols of cardiac differentiation have been established by essentially focusing on specific growth factors on human pluripotent stem cell (hPSC) differentiation efficiency. However, the optimal environmental factors to obtain cardiac myocytes in network are still unclear. The mesoderm germ layer differentiation is known to be enhanced by low oxygen exposure. Here, we hypothesized that low oxygen exposure enhances the molecular and functional maturity of the cardiomyocytes. We aimed at comparing the molecular and functional consequences of low (5% O-2 or LOE) and high oxygen exposure (21% O-2 or HOE) on cardiac differentiation of hPSCs in 2D- and 3D-based protocols. hPSC-CMs were differentiated through both the 2D (monolayer) and 3D (embryoid body) protocols using several lines. Cardiac marker expression and cell morphology were assessed. The mitochondrial localization and metabolic properties were evaluated. The intracellular Ca2+ handling and contractile properties were also monitored. The 2D cardiac monolayer can only be differentiated in HOE. The 3D cardiac spheroids containing hPSC-CMs in LOE further exhibited cardiac markers, hypertrophy, steadier SR Ca2+ release properties revealing a better SR Ca2+ handling, and enhanced contractile force. Preserved distribution of mitochondria and similar oxygen consumption by the mitochondrial respiratory chain complexes were also observed. Our results brought evidences that LOE is moderately beneficial for the 3D cardiac spheroids with hPSC-CMs exhibiting further maturity. In contrast, the 2D cardiac monolayers strictly require HOE.

Links

LM2018127, research and development project

Name: Česká infrastruktura pro integrativní strukturní biologii (Acronym: CIISB)

Investor: Ministry of Education, Youth and Sports of the CR

NU20-06-00156, research and development project

Name: Vliv pneumologické medikace na funkce lidských kardiomyocytů.

Investor: Ministry of Health of the CR, Subprogram 1 - standard

2SGA2744, interní kód MU

Name: CARDIOSTEM (Acronym: CARDIOSTEM)

Investor: South-Moravian Region, Incoming grants

90127, large research infrastructures

Name: CIISB II

Citovat

SOUIDI, M., Y. SLEIMAN, Ivana AĆIMOVIĆ, Jan PŘIBYL, A. CHARRABI, V. BAECKER, V. SCHEUERMANN, Martin PEŠL, Šárka JELÍNKOVÁ, Petr SKLÁDAL, Petr DVOŘÁK, A. LACAMPAGNE, Vladimír ROTREKL and A. C. MELI. Oxygen Is an Ambivalent Factor for the Differentiation of Human Pluripotent Stem Cells in Cardiac 2D Monolayer and 3D Cardiac Spheroids. International Journal of Molecular Sciences. Basel: Multidisciplinary Digital Publishing Institute, 2021, vol. 22, No 2, p. 1-19. ISSN 1422-0067. Available from: https://dx.doi.org/10.3390/ijms22020662.

@article{1787484,
   author = {Souidi, M. and Sleiman, Y. and Aćimović, Ivana and Přibyl, Jan and Charrabi, A. and Baecker, V. and Scheuermann, V. and Pešl, Martin and Jelínková, Šárka and Skládal, Petr and Dvořák, Petr and Lacampagne, A. and Rotrekl, Vladimír and Meli, A. C.},
   article_location = {Basel},
   article_number = {2},
   doi = {http://dx.doi.org/10.3390/ijms22020662},
   keywords = {hPSC-derived cardiomyocytes; cardiac spheroids; embryoid bodies; 2D-monolayer; oxygen exposure; intracellular calcium handling; mitochondrial oxygen consumption; contractile properties},
   language = {eng},
   issn = {1422-0067},
   journal = {International Journal of Molecular Sciences},
   title = {Oxygen Is an Ambivalent Factor for the Differentiation of Human Pluripotent Stem Cells in Cardiac 2D Monolayer and 3D Cardiac Spheroids},
   url = {https://www.mdpi.com/1422-0067/22/2/662},
   volume = {22},
   year = {2021}
}

TY  - JOUR
ID  - 1787484
AU  - Souidi, M. - Sleiman, Y. - Aćimović, Ivana - Přibyl, Jan - Charrabi, A. - Baecker, V. - Scheuermann, V. - Pešl, Martin - Jelínková, Šárka - Skládal, Petr - Dvořák, Petr - Lacampagne, A. - Rotrekl, Vladimír - Meli, A. C.
PY  - 2021
TI  - Oxygen Is an Ambivalent Factor for the Differentiation of Human Pluripotent Stem Cells in Cardiac 2D Monolayer and 3D Cardiac Spheroids
JF  - International Journal of Molecular Sciences
VL  - 22
IS  - 2
SP  - 1-19
EP  - 1-19
PB  - Multidisciplinary Digital Publishing Institute
SN  - 14220067
KW  - hPSC-derived cardiomyocytes
KW  - cardiac spheroids
KW  - embryoid bodies
KW  - 2D-monolayer
KW  - oxygen exposure
KW  - intracellular calcium handling
KW  - mitochondrial oxygen consumption
KW  - contractile properties
UR  - https://www.mdpi.com/1422-0067/22/2/662
N2  - Numerous protocols of cardiac differentiation have been established by essentially focusing on specific growth factors on human pluripotent stem cell (hPSC) differentiation efficiency. However, the optimal environmental factors to obtain cardiac myocytes in network are still unclear. The mesoderm germ layer differentiation is known to be enhanced by low oxygen exposure. Here, we hypothesized that low oxygen exposure enhances the molecular and functional maturity of the cardiomyocytes. We aimed at comparing the molecular and functional consequences of low (5% O-2 or LOE) and high oxygen exposure (21% O-2 or HOE) on cardiac differentiation of hPSCs in 2D- and 3D-based protocols. hPSC-CMs were differentiated through both the 2D (monolayer) and 3D (embryoid body) protocols using several lines. Cardiac marker expression and cell morphology were assessed. The mitochondrial localization and metabolic properties were evaluated. The intracellular Ca2+ handling and contractile properties were also monitored. The 2D cardiac monolayer can only be differentiated in HOE. The 3D cardiac spheroids containing hPSC-CMs in LOE further exhibited cardiac markers, hypertrophy, steadier SR Ca2+ release properties revealing a better SR Ca2+ handling, and enhanced contractile force. Preserved distribution of mitochondria and similar oxygen consumption by the mitochondrial respiratory chain complexes were also observed. Our results brought evidences that LOE is moderately beneficial for the 3D cardiac spheroids with hPSC-CMs exhibiting further maturity. In contrast, the 2D cardiac monolayers strictly require HOE.
ER  -

SOUIDI, M., Y. SLEIMAN, Ivana A$\backslash$'CIMOVI$\backslash$'C, Jan PŘIBYL, A. CHARRABI, V. BAECKER, V. SCHEUERMANN, Martin PEŠL, Šárka JELÍNKOVÁ, Petr SKLÁDAL, Petr DVOŘÁK, A. LACAMPAGNE, Vladimír ROTREKL and A. C. MELI. Oxygen Is an Ambivalent Factor for the Differentiation of Human Pluripotent Stem Cells in Cardiac 2D Monolayer and 3D Cardiac Spheroids. \textit{International Journal of Molecular Sciences}. Basel: Multidisciplinary Digital Publishing Institute, 2021, vol.~22, No~2, p.~1-19. ISSN~1422-0067. Available from: https://dx.doi.org/10.3390/ijms22020662.

Detailed Information on Publication Record