Toxicological Profile of Umbilical Cord Blood-Derived Small Extracellular Vesicles
Autor(a) principal: | |
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Data de Publicação: | 2021 |
Outros Autores: | , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
DOI: | 10.3390/membranes11090647 |
Texto Completo: | http://hdl.handle.net/10316/105226 https://doi.org/10.3390/membranes11090647 |
Resumo: | The development and adoption of cell therapies has been largely limited by difficulties associated with their safety, handling, and storage. Extracellular vesicles (EV) have recently emerged as a likely mediator for the therapeutic effect of cells, offering several advantages over cell therapies. Due to their small size and inability to expand and metastasize, EV are generally considered safer than cell transplantation. Nevertheless, few studies have scrutinized the toxicity profile of EV, particularly after repeated high-dose administration. The present study aimed to evaluate a preparation of small EV obtained from umbilical cord blood mononuclear cells (UCB-MNC-sEV) for its cytotoxicity in different cell lines, as well as its differential accumulation, distribution, and toxicity following repeated intravenous (IV) administrations in a rodent model. In vitro, repeated sEV exposure in concentrations up to 1 × 1011 particles/mL had no deleterious impact on the viability or metabolic activity of peripheral blood mononuclear cells, THP-1 monocytes, THP-1-derived macrophages, normal dermal human fibroblasts, or human umbilical vein endothelial cells. DiR-labelled sEV, injected intravenously for four weeks in healthy rats, were detected in clearance organs, particularly the kidneys, spleen, and liver, similarly to control dye. Moreover, repeated administrations for six and twelve weeks of up to 1 × 1010 total particles of sEV dye were well-tolerated, with no changes in general haematological cell counts, or kidney and liver toxicity markers. More importantly, unlabelled sEV likewise did not induce significant alterations in cellular and biochemical blood parameters, nor any morphological changes in the heart, kidney, lung, spleen, or liver tissue. In sum, our data show that UCB-MNC-sEV have no significant toxicity in vitro or in vivo, even when administered repeatedly at high concentrations, therefore confirming their safety profile and potential suitability for future clinical use. |
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Toxicological Profile of Umbilical Cord Blood-Derived Small Extracellular Vesiclesextracellular vesiclesumbilical cord bloodEV therapeuticsEV toxicityThe development and adoption of cell therapies has been largely limited by difficulties associated with their safety, handling, and storage. Extracellular vesicles (EV) have recently emerged as a likely mediator for the therapeutic effect of cells, offering several advantages over cell therapies. Due to their small size and inability to expand and metastasize, EV are generally considered safer than cell transplantation. Nevertheless, few studies have scrutinized the toxicity profile of EV, particularly after repeated high-dose administration. The present study aimed to evaluate a preparation of small EV obtained from umbilical cord blood mononuclear cells (UCB-MNC-sEV) for its cytotoxicity in different cell lines, as well as its differential accumulation, distribution, and toxicity following repeated intravenous (IV) administrations in a rodent model. In vitro, repeated sEV exposure in concentrations up to 1 × 1011 particles/mL had no deleterious impact on the viability or metabolic activity of peripheral blood mononuclear cells, THP-1 monocytes, THP-1-derived macrophages, normal dermal human fibroblasts, or human umbilical vein endothelial cells. DiR-labelled sEV, injected intravenously for four weeks in healthy rats, were detected in clearance organs, particularly the kidneys, spleen, and liver, similarly to control dye. Moreover, repeated administrations for six and twelve weeks of up to 1 × 1010 total particles of sEV dye were well-tolerated, with no changes in general haematological cell counts, or kidney and liver toxicity markers. More importantly, unlabelled sEV likewise did not induce significant alterations in cellular and biochemical blood parameters, nor any morphological changes in the heart, kidney, lung, spleen, or liver tissue. In sum, our data show that UCB-MNC-sEV have no significant toxicity in vitro or in vivo, even when administered repeatedly at high concentrations, therefore confirming their safety profile and potential suitability for future clinical use.MDPI2021-08-24info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://hdl.handle.net/10316/105226http://hdl.handle.net/10316/105226https://doi.org/10.3390/membranes11090647eng2077-0375Rodrigues, Sílvia C.Cardoso, Renato M. S.Gomes, Claudia F.Duarte, Filipe ValenteFreire, Patricia C.Neves, RicardoCorreia, Joana Simõesinfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-02-09T13:27:29Zoai:estudogeral.uc.pt:10316/105226Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T21:21:49.697055Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Toxicological Profile of Umbilical Cord Blood-Derived Small Extracellular Vesicles |
title |
Toxicological Profile of Umbilical Cord Blood-Derived Small Extracellular Vesicles |
spellingShingle |
Toxicological Profile of Umbilical Cord Blood-Derived Small Extracellular Vesicles Toxicological Profile of Umbilical Cord Blood-Derived Small Extracellular Vesicles Rodrigues, Sílvia C. extracellular vesicles umbilical cord blood EV therapeutics EV toxicity Rodrigues, Sílvia C. extracellular vesicles umbilical cord blood EV therapeutics EV toxicity |
title_short |
Toxicological Profile of Umbilical Cord Blood-Derived Small Extracellular Vesicles |
title_full |
Toxicological Profile of Umbilical Cord Blood-Derived Small Extracellular Vesicles |
title_fullStr |
Toxicological Profile of Umbilical Cord Blood-Derived Small Extracellular Vesicles Toxicological Profile of Umbilical Cord Blood-Derived Small Extracellular Vesicles |
title_full_unstemmed |
Toxicological Profile of Umbilical Cord Blood-Derived Small Extracellular Vesicles Toxicological Profile of Umbilical Cord Blood-Derived Small Extracellular Vesicles |
title_sort |
Toxicological Profile of Umbilical Cord Blood-Derived Small Extracellular Vesicles |
author |
Rodrigues, Sílvia C. |
author_facet |
Rodrigues, Sílvia C. Rodrigues, Sílvia C. Cardoso, Renato M. S. Gomes, Claudia F. Duarte, Filipe Valente Freire, Patricia C. Neves, Ricardo Correia, Joana Simões Cardoso, Renato M. S. Gomes, Claudia F. Duarte, Filipe Valente Freire, Patricia C. Neves, Ricardo Correia, Joana Simões |
author_role |
author |
author2 |
Cardoso, Renato M. S. Gomes, Claudia F. Duarte, Filipe Valente Freire, Patricia C. Neves, Ricardo Correia, Joana Simões |
author2_role |
author author author author author author |
dc.contributor.author.fl_str_mv |
Rodrigues, Sílvia C. Cardoso, Renato M. S. Gomes, Claudia F. Duarte, Filipe Valente Freire, Patricia C. Neves, Ricardo Correia, Joana Simões |
dc.subject.por.fl_str_mv |
extracellular vesicles umbilical cord blood EV therapeutics EV toxicity |
topic |
extracellular vesicles umbilical cord blood EV therapeutics EV toxicity |
description |
The development and adoption of cell therapies has been largely limited by difficulties associated with their safety, handling, and storage. Extracellular vesicles (EV) have recently emerged as a likely mediator for the therapeutic effect of cells, offering several advantages over cell therapies. Due to their small size and inability to expand and metastasize, EV are generally considered safer than cell transplantation. Nevertheless, few studies have scrutinized the toxicity profile of EV, particularly after repeated high-dose administration. The present study aimed to evaluate a preparation of small EV obtained from umbilical cord blood mononuclear cells (UCB-MNC-sEV) for its cytotoxicity in different cell lines, as well as its differential accumulation, distribution, and toxicity following repeated intravenous (IV) administrations in a rodent model. In vitro, repeated sEV exposure in concentrations up to 1 × 1011 particles/mL had no deleterious impact on the viability or metabolic activity of peripheral blood mononuclear cells, THP-1 monocytes, THP-1-derived macrophages, normal dermal human fibroblasts, or human umbilical vein endothelial cells. DiR-labelled sEV, injected intravenously for four weeks in healthy rats, were detected in clearance organs, particularly the kidneys, spleen, and liver, similarly to control dye. Moreover, repeated administrations for six and twelve weeks of up to 1 × 1010 total particles of sEV dye were well-tolerated, with no changes in general haematological cell counts, or kidney and liver toxicity markers. More importantly, unlabelled sEV likewise did not induce significant alterations in cellular and biochemical blood parameters, nor any morphological changes in the heart, kidney, lung, spleen, or liver tissue. In sum, our data show that UCB-MNC-sEV have no significant toxicity in vitro or in vivo, even when administered repeatedly at high concentrations, therefore confirming their safety profile and potential suitability for future clinical use. |
publishDate |
2021 |
dc.date.none.fl_str_mv |
2021-08-24 |
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.uri.fl_str_mv |
http://hdl.handle.net/10316/105226 http://hdl.handle.net/10316/105226 https://doi.org/10.3390/membranes11090647 |
url |
http://hdl.handle.net/10316/105226 https://doi.org/10.3390/membranes11090647 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
2077-0375 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.publisher.none.fl_str_mv |
MDPI |
publisher.none.fl_str_mv |
MDPI |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
instacron_str |
RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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1822183293646274560 |
dc.identifier.doi.none.fl_str_mv |
10.3390/membranes11090647 |