A Novel High-Content Screening-Based Method for Anti- Trypanosoma cruzi Drug Discovery Using Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes

Portella, Diogo Crispim Nascimento; Rossi, Erik Aranha; Paredes, Bruno Diaz; Bastos, Tanira Matutino; Meira, Cássio Santana; Nonaka, Carolina Vasques Kymie; Silva, Daniela Nascimento; Caria, Alex Improta; Moreira, Diogo Rodrigo Magalhaes; Leite, Ana Cristina Lima; Oliveira Filho, Gevanio Bezerra de; Barbosa Filho, José Maria; Santos, Ricardo Ribeiro dos; Soares, Milena Botelho Pereira; Souza, Bruno Solano de Freita

A Novel High-Content Screening-Based Method for Anti- Trypanosoma cruzi Drug Discovery Using Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes

Detalhes bibliográficos
Autor(a) principal:	Portella, Diogo Crispim Nascimento
Data de Publicação:	2021
Outros Autores:	Rossi, Erik Aranha, Paredes, Bruno Diaz, Bastos, Tanira Matutino, Meira, Cássio Santana, Nonaka, Carolina Vasques Kymie, Silva, Daniela Nascimento, Caria, Alex Improta, Moreira, Diogo Rodrigo Magalhaes, Leite, Ana Cristina Lima, Oliveira Filho, Gevanio Bezerra de, Barbosa Filho, José Maria, Santos, Ricardo Ribeiro dos, Soares, Milena Botelho Pereira, Souza, Bruno Solano de Freita
Tipo de documento:	Artigo
Idioma:	eng
Título da fonte:	Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo:	https://www.arca.fiocruz.br/handle/icict/49134
Resumo:	CNPq, FAPESB, and FINEP.

Metadados do item

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oai_identifier_str	oai:www.arca.fiocruz.br:icict/49134
network_acronym_str	CRUZ
network_name_str	Repositório Institucional da FIOCRUZ (ARCA)
repository_id_str	2135
spelling	Portella, Diogo Crispim NascimentoRossi, Erik AranhaParedes, Bruno DiazBastos, Tanira MatutinoMeira, Cássio SantanaNonaka, Carolina Vasques KymieSilva, Daniela NascimentoCaria, Alex ImprotaMoreira, Diogo Rodrigo MagalhaesLeite, Ana Cristina LimaOliveira Filho, Gevanio Bezerra deBarbosa Filho, José MariaSantos, Ricardo Ribeiro dosSoares, Milena Botelho PereiraSouza, Bruno Solano de Freita2021-09-22T17:38:41Z2021-09-22T17:38:41Z2021PORTELLA, Diogo Crispim Nascimento et al. A Novel High-Content Screening-Based Method for Anti- Trypanosoma cruzi Drug Discovery Using Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes. Stem Cells International, 2021.1687-966Xhttps://www.arca.fiocruz.br/handle/icict/4913410.1155/2021/2642807CNPq, FAPESB, and FINEP."Múltipla ver em Notas"Chagas disease is caused by Trypanosoma cruzi infection and remains a relevant cause of chronic heart failure in Latin America. The pharmacological arsenal for Chagas disease is limited, and the available anti-T. cruzi drugs are not effective when administered during the chronic phase. Cardiomyocytes derived from human-induced pluripotent stem cells (hiPSC-CMs) have the potential to accelerate the process of drug discovery for Chagas disease, through predictive preclinical assays in target human cells. Here, we aimed to establish a novel high-content screening- (HCS-) based method using hiPSC-CMs to simultaneously evaluate anti-T. cruzi activity and cardiotoxicity of chemical compounds. To provide proof-of-concept data, the reference drug benznidazole and three compounds with known anti-T. cruzi activity (a betulinic acid derivative named BA5 and two thiazolidinone compounds named GT5A and GT5B) were evaluated in the assay. hiPSC-CMs were infected with T. cruzi and incubated for 48 h with serial dilutions of the compounds for determination of EC50 and CC50 values. Automated multiparametric analyses were performed using an automated high-content imaging system. Sublethal toxicity measurements were evaluated through morphological measurements related to the integrity of the cytoskeleton by phalloidin staining, nuclear score by Hoechst 33342 staining, mitochondria score following MitoTracker staining, and quantification of NT-pro-BNP, a peptide released upon mechanical myocardial stress. The compounds showed EC50 values for anti-T. cruzi activity similar to those previously described for other cell types, and GT5B showed a pronounced trypanocidal activity in hiPSC-CMs. Sublethal changes in cytoskeletal and nucleus scores correlated with NT-pro-BNP levels in the culture supernatant. Mitochondrial score changes were associated with increased cytotoxicity. The assay was feasible and allowed rapid assessment of anti-T. cruzi action of the compounds, in addition to cardiotoxicity parameters. The utilization of hiPSC-CMs in the drug development workflow for Chagas disease may help in the identification of novel compoundsengHindawiTrypanosoma cruziDoença de ChagasInsuficiência CardíacaCardiotoxicidadeCélulas-Tronco Pluripotentes InduzidasTrypanosoma cruziChagas' diseaseCardiac insufficiencyCardiotoxicityInduced Pluripotent Stem CellsA Novel High-Content Screening-Based Method for Anti- Trypanosoma cruzi Drug Discovery Using Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytesinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-83097https://www.arca.fiocruz.br/bitstream/icict/49134/1/license.txt36b51ef91c52b5338d9d29ba0cc807bcMD51ORIGINALPortella, Diogo Crispim Nascimento A Novel High Content....pdfPortella, Diogo Crispim Nascimento A Novel High Content....pdfapplication/pdf7044954https://www.arca.fiocruz.br/bitstream/icict/49134/2/Portella%2c%20Diogo%20Crispim%20Nascimento%20A%20Novel%20High%20Content....pdfb5eb32b20c9dbfb3bf0b51b982fe9901MD52icict/491342023-03-15 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dc.title.pt_BR.fl_str_mv	A Novel High-Content Screening-Based Method for Anti- Trypanosoma cruzi Drug Discovery Using Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes
title	A Novel High-Content Screening-Based Method for Anti- Trypanosoma cruzi Drug Discovery Using Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes
spellingShingle	A Novel High-Content Screening-Based Method for Anti- Trypanosoma cruzi Drug Discovery Using Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes Portella, Diogo Crispim Nascimento Trypanosoma cruzi Doença de Chagas Insuficiência Cardíaca Cardiotoxicidade Células-Tronco Pluripotentes Induzidas Trypanosoma cruzi Chagas' disease Cardiac insufficiency Cardiotoxicity Induced Pluripotent Stem Cells
title_short	A Novel High-Content Screening-Based Method for Anti- Trypanosoma cruzi Drug Discovery Using Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes
title_full	A Novel High-Content Screening-Based Method for Anti- Trypanosoma cruzi Drug Discovery Using Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes
title_fullStr	A Novel High-Content Screening-Based Method for Anti- Trypanosoma cruzi Drug Discovery Using Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes
title_full_unstemmed	A Novel High-Content Screening-Based Method for Anti- Trypanosoma cruzi Drug Discovery Using Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes
title_sort	A Novel High-Content Screening-Based Method for Anti- Trypanosoma cruzi Drug Discovery Using Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes
author	Portella, Diogo Crispim Nascimento
author_facet	Portella, Diogo Crispim Nascimento Rossi, Erik Aranha Paredes, Bruno Diaz Bastos, Tanira Matutino Meira, Cássio Santana Nonaka, Carolina Vasques Kymie Silva, Daniela Nascimento Caria, Alex Improta Moreira, Diogo Rodrigo Magalhaes Leite, Ana Cristina Lima Oliveira Filho, Gevanio Bezerra de Barbosa Filho, José Maria Santos, Ricardo Ribeiro dos Soares, Milena Botelho Pereira Souza, Bruno Solano de Freita
author_role	author
author2	Rossi, Erik Aranha Paredes, Bruno Diaz Bastos, Tanira Matutino Meira, Cássio Santana Nonaka, Carolina Vasques Kymie Silva, Daniela Nascimento Caria, Alex Improta Moreira, Diogo Rodrigo Magalhaes Leite, Ana Cristina Lima Oliveira Filho, Gevanio Bezerra de Barbosa Filho, José Maria Santos, Ricardo Ribeiro dos Soares, Milena Botelho Pereira Souza, Bruno Solano de Freita
author2_role	author author author author author author author author author author author author author author
dc.contributor.author.fl_str_mv	Portella, Diogo Crispim Nascimento Rossi, Erik Aranha Paredes, Bruno Diaz Bastos, Tanira Matutino Meira, Cássio Santana Nonaka, Carolina Vasques Kymie Silva, Daniela Nascimento Caria, Alex Improta Moreira, Diogo Rodrigo Magalhaes Leite, Ana Cristina Lima Oliveira Filho, Gevanio Bezerra de Barbosa Filho, José Maria Santos, Ricardo Ribeiro dos Soares, Milena Botelho Pereira Souza, Bruno Solano de Freita
dc.subject.other.pt_BR.fl_str_mv	Trypanosoma cruzi Doença de Chagas Insuficiência Cardíaca Cardiotoxicidade Células-Tronco Pluripotentes Induzidas
topic	Trypanosoma cruzi Doença de Chagas Insuficiência Cardíaca Cardiotoxicidade Células-Tronco Pluripotentes Induzidas Trypanosoma cruzi Chagas' disease Cardiac insufficiency Cardiotoxicity Induced Pluripotent Stem Cells
dc.subject.en.pt_BR.fl_str_mv	Trypanosoma cruzi Chagas' disease Cardiac insufficiency Cardiotoxicity Induced Pluripotent Stem Cells
description	CNPq, FAPESB, and FINEP.
publishDate	2021
dc.date.accessioned.fl_str_mv	2021-09-22T17:38:41Z
dc.date.available.fl_str_mv	2021-09-22T17:38:41Z
dc.date.issued.fl_str_mv	2021
dc.type.status.fl_str_mv	info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv	info:eu-repo/semantics/article
format	article
status_str	publishedVersion
dc.identifier.citation.fl_str_mv	PORTELLA, Diogo Crispim Nascimento et al. A Novel High-Content Screening-Based Method for Anti- Trypanosoma cruzi Drug Discovery Using Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes. Stem Cells International, 2021.
dc.identifier.uri.fl_str_mv	https://www.arca.fiocruz.br/handle/icict/49134
dc.identifier.issn.pt_BR.fl_str_mv	1687-966X
dc.identifier.doi.none.fl_str_mv	10.1155/2021/2642807
identifier_str_mv	PORTELLA, Diogo Crispim Nascimento et al. A Novel High-Content Screening-Based Method for Anti- Trypanosoma cruzi Drug Discovery Using Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes. Stem Cells International, 2021. 1687-966X 10.1155/2021/2642807
url	https://www.arca.fiocruz.br/handle/icict/49134
dc.language.iso.fl_str_mv	eng
language	eng
dc.rights.driver.fl_str_mv	info:eu-repo/semantics/openAccess
eu_rights_str_mv	openAccess
dc.publisher.none.fl_str_mv	Hindawi
publisher.none.fl_str_mv	Hindawi
dc.source.none.fl_str_mv	reponame:Repositório Institucional da FIOCRUZ (ARCA) instname:Fundação Oswaldo Cruz (FIOCRUZ) instacron:FIOCRUZ
instname_str	Fundação Oswaldo Cruz (FIOCRUZ)
instacron_str	FIOCRUZ
institution	FIOCRUZ
reponame_str	Repositório Institucional da FIOCRUZ (ARCA)
collection	Repositório Institucional da FIOCRUZ (ARCA)
bitstream.url.fl_str_mv	https://www.arca.fiocruz.br/bitstream/icict/49134/1/license.txt https://www.arca.fiocruz.br/bitstream/icict/49134/2/Portella%2c%20Diogo%20Crispim%20Nascimento%20A%20Novel%20High%20Content....pdf
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bitstream.checksumAlgorithm.fl_str_mv	MD5 MD5
repository.name.fl_str_mv	Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)
repository.mail.fl_str_mv	repositorio.arca@fiocruz.br
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A Novel High-Content Screening-Based Method for Anti- Trypanosoma cruzi Drug Discovery Using Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes

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