Generation and maturation of human iPSC-derived 3D organotypic
cardiac microtissues in long-term culture

J 2022

Generation and maturation of human iPSC-derived 3D organotypic cardiac microtissues in long-term culture

ERGIR, Ece, la Cruz Jorge OLIVER-DE, Soraia FERNANDES, Marco CASSANI, Francesco NIRO et. al.

Basic information

Original name

Generation and maturation of human iPSC-derived 3D organotypic cardiac microtissues in long-term culture

Authors

ERGIR, Ece, la Cruz Jorge OLIVER-DE, Soraia FERNANDES, Marco CASSANI, Francesco NIRO (380 Italy, belonging to the institution), Daniel PEREIRA DE SOUSA (620 Portugal, belonging to the institution), Jan VRBSKY (203 Czech Republic), Vladimir VINARSKY (203 Czech Republic), Ana Rubina PERESTRELO, Doriana DEBELLIS, Natália VADOVIČOVÁ (203 Czech Republic, belonging to the institution), Stjepan ULDRIJAN (203 Czech Republic, belonging to the institution), Francesca CAVALIERI, Stefania PAGLIARI, Heinz REDL, Peter ERTL and Giancarlo FORTE

Edition

Nature Scientific Reports, Berlin, NATURE RESEARCH, 2022, 2045-2322

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10601 Cell biology

Country of publisher

Germany

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 4.600

RIV identification code

RIV/00216224:14110/22:00128442

Organization unit

Faculty of Medicine

DOI

http://dx.doi.org/10.1038/s41598-022-22225-w

UT WoS

000869897200017

Keywords in English

3D organotypic cardiac microtissues; iPSC

Abstract

V originále

Cardiovascular diseases remain the leading cause of death worldwide; hence there is an increasing focus on developing physiologically relevant in vitro cardiovascular tissue models suitable for studying personalized medicine and pre-clinical tests. Despite recent advances, models that reproduce both tissue complexity and maturation are still limited. We have established a scaffold-free protocol to generate multicellular, beating human cardiac microtissues in vitro from hiPSCs-namely human organotypic cardiac microtissues (hOCMTs)-that show some degree of self-organization and can be cultured for long term. This is achieved by the differentiation of hiPSC in 2D monolayer culture towards cardiovascular lineage, followed by further aggregation on low-attachment culture dishes in 3D. The generated hOCMTs contain multiple cell types that physiologically compose the heart and beat without external stimuli for more than 100 days. We have shown that 3D hOCMTs display improved cardiac specification, survival and metabolic maturation as compared to standard monolayer cardiac differentiation. We also confirmed the functionality of hOCMTs by their response to cardioactive drugs in long-term culture. Furthermore, we demonstrated that they could be used to study chemotherapy-induced cardiotoxicity. Due to showing a tendency for self-organization, cellular heterogeneity, and functionality in our 3D microtissues over extended culture time, we could also confirm these constructs as human cardiac organoids (hCOs). This study could help to develop more physiologically-relevant cardiac tissue models, and represent a powerful platform for future translational research in cardiovascular biology.

Links

LM2018132, research and development project

Name: Národní centrum lékařské genomiky (Acronym: NCLG)

Investor: Ministry of Education, Youth and Sports of the CR, National Center for Medical Genomics

Citovat

ERGIR, Ece, la Cruz Jorge OLIVER-DE, Soraia FERNANDES, Marco CASSANI, Francesco NIRO, Daniel PEREIRA DE SOUSA, Jan VRBSKY, Vladimir VINARSKY, Ana Rubina PERESTRELO, Doriana DEBELLIS, Natália VADOVIČOVÁ, Stjepan ULDRIJAN, Francesca CAVALIERI, Stefania PAGLIARI, Heinz REDL, Peter ERTL and Giancarlo FORTE. Generation and maturation of human iPSC-derived 3D organotypic cardiac microtissues in long-term culture. Nature Scientific Reports. Berlin: NATURE RESEARCH, 2022, vol. 12, No 1, p. 1-21. ISSN 2045-2322. Available from: https://dx.doi.org/10.1038/s41598-022-22225-w.

@article{2251439,
   author = {Ergir, Ece and OliverandDe, la Cruz Jorge and Fernandes, Soraia and Cassani, Marco and Niro, Francesco and Pereira de Sousa, Daniel and Vrbsky, Jan and Vinarsky, Vladimir and Perestrelo, Ana Rubina and Debellis, Doriana and Vadovičová, Natália and Uldrijan, Stjepan and Cavalieri, Francesca and Pagliari, Stefania and Redl, Heinz and Ertl, Peter and Forte, Giancarlo},
   article_location = {Berlin},
   article_number = {1},
   doi = {http://dx.doi.org/10.1038/s41598-022-22225-w},
   keywords = {3D organotypic cardiac microtissues; iPSC},
   language = {eng},
   issn = {2045-2322},
   journal = {Nature Scientific Reports},
   title = {Generation and maturation of human iPSC-derived 3D organotypic cardiac microtissues in long-term culture},
   url = {https://www.nature.com/articles/s41598-022-22225-w},
   volume = {12},
   year = {2022}
}

TY  - JOUR
ID  - 2251439
AU  - Ergir, Ece - Oliver-De, la Cruz Jorge - Fernandes, Soraia - Cassani, Marco - Niro, Francesco - Pereira de Sousa, Daniel - Vrbsky, Jan - Vinarsky, Vladimir - Perestrelo, Ana Rubina - Debellis, Doriana - Vadovičová, Natália - Uldrijan, Stjepan - Cavalieri, Francesca - Pagliari, Stefania - Redl, Heinz - Ertl, Peter - Forte, Giancarlo
PY  - 2022
TI  - Generation and maturation of human iPSC-derived 3D organotypic cardiac microtissues in long-term culture
JF  - Nature Scientific Reports
VL  - 12
IS  - 1
SP  - 1-21
EP  - 1-21
PB  - NATURE RESEARCH
SN  - 20452322
KW  - 3D organotypic cardiac microtissues
KW  - iPSC
UR  - https://www.nature.com/articles/s41598-022-22225-w
N2  - Cardiovascular diseases remain the leading cause of death worldwide; hence there is an increasing focus on developing physiologically relevant in vitro cardiovascular tissue models suitable for studying personalized medicine and pre-clinical tests. Despite recent advances, models that reproduce both tissue complexity and maturation are still limited. We have established a scaffold-free protocol to generate multicellular, beating human cardiac microtissues in vitro from hiPSCs-namely human organotypic cardiac microtissues (hOCMTs)-that show some degree of self-organization and can be cultured for long term. This is achieved by the differentiation of hiPSC in 2D monolayer culture towards cardiovascular lineage, followed by further aggregation on low-attachment culture dishes in 3D. The generated hOCMTs contain multiple cell types that physiologically compose the heart and beat without external stimuli for more than 100 days. We have shown that 3D hOCMTs display improved cardiac specification, survival and metabolic maturation as compared to standard monolayer cardiac differentiation. We also confirmed the functionality of hOCMTs by their response to cardioactive drugs in long-term culture. Furthermore, we demonstrated that they could be used to study chemotherapy-induced cardiotoxicity. Due to showing a tendency for self-organization, cellular heterogeneity, and functionality in our 3D microtissues over extended culture time, we could also confirm these constructs as human cardiac organoids (hCOs). This study could help to develop more physiologically-relevant cardiac tissue models, and represent a powerful platform for future translational research in cardiovascular biology.
ER  -

ERGIR, Ece, la Cruz Jorge OLIVER-DE, Soraia FERNANDES, Marco CASSANI, Francesco NIRO, Daniel PEREIRA DE SOUSA, Jan VRBSKY, Vladimir VINARSKY, Ana Rubina PERESTRELO, Doriana DEBELLIS, Natália VADOVIČOVÁ, Stjepan ULDRIJAN, Francesca CAVALIERI, Stefania PAGLIARI, Heinz REDL, Peter ERTL and Giancarlo FORTE. Generation and maturation of human iPSC-derived 3D organotypic cardiac microtissues in long-term culture. \textit{Nature Scientific Reports}. Berlin: NATURE RESEARCH, 2022, vol.~12, No~1, p.~1-21. ISSN~2045-2322. Available from: https://dx.doi.org/10.1038/s41598-022-22225-w.

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