Potencial terapêutico cardíaco das células tronco mesenquimais precursoras de medula óssea CD271+

Detalhes bibliográficos
Autor(a) principal: Zuttion, Marilia Sanches Santos Rizzo [UNIFESP]
Data de Publicação: 2018
Tipo de documento: Tese
Idioma: por
Título da fonte: Repositório Institucional da UNIFESP
Texto Completo: https://sucupira.capes.gov.br/sucupira/public/consultas/coleta/trabalhoConclusao/viewTrabalhoConclusao.jsf?popup=true&id_trabalho=7023888
https://repositorio.unifesp.br/handle/11600/52334
Resumo: MSCs are a particularly promising bone marrow-derived cell for cardiac regenerative therapy because of their availability, immunologic properties, and record of safety and efficacy. Several studies have confirmed the specificity of CD271 on MSC isolated from bone marrow. This marker has been suggested as a versatile marker to selectively isolate multipotent MSC with both immunosuppressive and lymphohematopoietic engraftment-promoting properties. Moreover MSC are preferentially selected in the CD271+ fraction compared to the CD271− fraction. Objective: We hypothesized that CD271+ MSCs isolated from normal human BM will repair ischemic heart damage in a mouse myocardial infarction (MI) model. Methods: CD271+ cells were isolated and injected in NOD/SCID mice following induction of a myocardial infarction (MI) and the effects on cardiac function and hemodynamic were determined by echocardiography and PV loop, respectively. MI size was calculated by dividing the length of MI, defined as the region with >50% of myocardial wall thickness with collagen (blue) deposition with left ventricle length through MIQuant software and the human injected CD271+ cells were tracked by immunofluorescence using anti-human mitochondrial ribosomal protein L11. The data were performed using the SIGMAPLOT software and the values were expressed as mean±standard error of the mean (SEM). The level of statistical significance was set at p<0.05.Results: The CD271+ cells were capable to adhere at the plastic and showed a high capacity of expansion in vitro. Culture of the CD271+ cells under adherent conditions were not able to differentiate in osteo and adipogenic lineages. Animals treated with CD271+ cells had no significant improvement in heart function, however it demonstrated a tendency to preserve EF. Moreover, it was possible to track human cells at the infarcted zone in cell treated animals. Conclusion: We conclude that CD271 inhibited the differentiation of this cells into osteo and adipogenic lineages. These results indicate a role for CD271 in inhibiting the differentiation of MSC CD271+ and the intracardiac injected CD271+ MSC were able to home to infarcted zone after 8 weeks post-MI and demonstrate a trend to preserve EF.
id UFSP_c2d92f64fa63fa3602c51dcdbeda4d59
oai_identifier_str oai:repositorio.unifesp.br/:11600/52334
network_acronym_str UFSP
network_name_str Repositório Institucional da UNIFESP
repository_id_str 3465
spelling Potencial terapêutico cardíaco das células tronco mesenquimais precursoras de medula óssea CD271+Cardiac therapeutic potential of bone marrow CD271+ MSC precursor cellTrunk cell of bone marrowCD271 + Trunk CellMyocardial infarctionCélula tronco de medula ósseaCélula tronco CD271+Infarto do miocárdioMSCs are a particularly promising bone marrow-derived cell for cardiac regenerative therapy because of their availability, immunologic properties, and record of safety and efficacy. Several studies have confirmed the specificity of CD271 on MSC isolated from bone marrow. This marker has been suggested as a versatile marker to selectively isolate multipotent MSC with both immunosuppressive and lymphohematopoietic engraftment-promoting properties. Moreover MSC are preferentially selected in the CD271+ fraction compared to the CD271− fraction. Objective: We hypothesized that CD271+ MSCs isolated from normal human BM will repair ischemic heart damage in a mouse myocardial infarction (MI) model. Methods: CD271+ cells were isolated and injected in NOD/SCID mice following induction of a myocardial infarction (MI) and the effects on cardiac function and hemodynamic were determined by echocardiography and PV loop, respectively. MI size was calculated by dividing the length of MI, defined as the region with >50% of myocardial wall thickness with collagen (blue) deposition with left ventricle length through MIQuant software and the human injected CD271+ cells were tracked by immunofluorescence using anti-human mitochondrial ribosomal protein L11. The data were performed using the SIGMAPLOT software and the values were expressed as mean±standard error of the mean (SEM). The level of statistical significance was set at p<0.05.Results: The CD271+ cells were capable to adhere at the plastic and showed a high capacity of expansion in vitro. Culture of the CD271+ cells under adherent conditions were not able to differentiate in osteo and adipogenic lineages. Animals treated with CD271+ cells had no significant improvement in heart function, however it demonstrated a tendency to preserve EF. Moreover, it was possible to track human cells at the infarcted zone in cell treated animals. Conclusion: We conclude that CD271 inhibited the differentiation of this cells into osteo and adipogenic lineages. These results indicate a role for CD271 in inhibiting the differentiation of MSC CD271+ and the intracardiac injected CD271+ MSC were able to home to infarcted zone after 8 weeks post-MI and demonstrate a trend to preserve EF.As CTM derivadas da medula óssea são células particularmente promissoras para a terapia regenerativa cardíaca pela sua disponibilidade, propriedades imunológicas e segurança e eficácia. Vários estudos confirmaram a especificidade do CD271 nas CTM isoladas da medula óssea. Este marcador foi sugerido como um marcador versátil para isolar seletivamente as CTM multipotente com propriedades imunossupressoras e promotoras do enxerto linfohematopoiético. Além disso, as CTM são preferencialmente selecionadas na fração CD271+ em comparação com a fração CD271-. Objetivo: Avaliar as CTM CD271+ isoladas da MO humana saudável em reparar danos cardíacos isquêmicos em um modelo de infarto do miocárdio (MI). Métodos: As células CD271+ foram isoladas e injetadas em camundongos NOD / SCID após a indução do IM e a função e hemodinâmica cardíaca foram determinados por ecocardiografia e PV loop, respectivamente. O IM foi determinado dividindo o comprimento do IM, definido como a região com> 50% de espessura da parede do miocárdio com deposição de colágeno (azul) com o comprimento do ventrículo esquerdo através do software MIQuant. As células humanas CD271+ injetadas foram rastreadas por imunofluorescência utilizando o anticorpo mitocôndria anti-humana proteína ribossômica L11. Os dados foram analisados utilizando o software SIGMAPLOT e os valores foram expressos como média ± erro padrão da média (SEM). O nível de significância estatística foi estabelecido em p<0,05. Resultados: As células CD271+ foram capazes de aderir rapidamente ao plástico e apresentaram alta capacidade de expansão in vitro. O cultivo das células CD271+ em condições aderentes não foi capaz de se diferenciar em linhagens óssea e adipogênica. Animais tratados com células CD271+ após IM não apresentaram melhora significativa na função cardíaca, porém demonstraram uma tendência em preservar fração de ejeção (FE). Além disso, foi possível rastrear células humanas na zona infartada em animais tratados com células pelo ensaio de imunofluorescência . Conclusão: Concluímos que o CD271 inibiu a diferenciação dessas células em linhagens osteo e adipogênica indicando um papel do CD271 na manutenção do status indiferenciado de CTM CD271+. Além disso, CTM CD271+ injetadas diretamente no coração foram capazes de enxertar a zona infartada após 8 semanas e demonstraram tendência em preservar FE.Dados abertos - Sucupira - Teses e dissertações (2018)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Universidade Federal de São Paulo (UNIFESP)Kerkis, Irina [UNIFESP]http://lattes.cnpq.br/4302687618153569http://lattes.cnpq.br/2793231976810653Universidade Federal de São Paulo (UNIFESP)Zuttion, Marilia Sanches Santos Rizzo [UNIFESP]2020-03-25T11:43:44Z2020-03-25T11:43:44Z2018-03-29info:eu-repo/semantics/doctoralThesisinfo:eu-repo/semantics/publishedVersion90 f.application/pdfhttps://sucupira.capes.gov.br/sucupira/public/consultas/coleta/trabalhoConclusao/viewTrabalhoConclusao.jsf?popup=true&id_trabalho=7023888ZUTTION, Marilia Sanches Santos Rizzo. Potencial terapêutico cardíaco das células tronco mesenquimais precursoras de medula óssea C D271+. 2018. 150 f. Tese (Doutorado em Biologia Estrutural e Funcional) - Escola Paulista de Medicina, Universidade Federal de S ão Paulo, São Paulo, 2018.2018-0266.pdfhttps://repositorio.unifesp.br/handle/11600/52334porSão Pauloinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UNIFESPinstname:Universidade Federal de São Paulo (UNIFESP)instacron:UNIFESP2024-08-02T14:15:08Zoai:repositorio.unifesp.br/:11600/52334Repositório InstitucionalPUBhttp://www.repositorio.unifesp.br/oai/requestbiblioteca.csp@unifesp.bropendoar:34652024-08-02T14:15:08Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)false
dc.title.none.fl_str_mv Potencial terapêutico cardíaco das células tronco mesenquimais precursoras de medula óssea CD271+
Cardiac therapeutic potential of bone marrow CD271+ MSC precursor cell
title Potencial terapêutico cardíaco das células tronco mesenquimais precursoras de medula óssea CD271+
spellingShingle Potencial terapêutico cardíaco das células tronco mesenquimais precursoras de medula óssea CD271+
Zuttion, Marilia Sanches Santos Rizzo [UNIFESP]
Trunk cell of bone marrow
CD271 + Trunk Cell
Myocardial infarction
Célula tronco de medula óssea
Célula tronco CD271+
Infarto do miocárdio
title_short Potencial terapêutico cardíaco das células tronco mesenquimais precursoras de medula óssea CD271+
title_full Potencial terapêutico cardíaco das células tronco mesenquimais precursoras de medula óssea CD271+
title_fullStr Potencial terapêutico cardíaco das células tronco mesenquimais precursoras de medula óssea CD271+
title_full_unstemmed Potencial terapêutico cardíaco das células tronco mesenquimais precursoras de medula óssea CD271+
title_sort Potencial terapêutico cardíaco das células tronco mesenquimais precursoras de medula óssea CD271+
author Zuttion, Marilia Sanches Santos Rizzo [UNIFESP]
author_facet Zuttion, Marilia Sanches Santos Rizzo [UNIFESP]
author_role author
dc.contributor.none.fl_str_mv Kerkis, Irina [UNIFESP]
http://lattes.cnpq.br/4302687618153569
http://lattes.cnpq.br/2793231976810653
Universidade Federal de São Paulo (UNIFESP)
dc.contributor.author.fl_str_mv Zuttion, Marilia Sanches Santos Rizzo [UNIFESP]
dc.subject.por.fl_str_mv Trunk cell of bone marrow
CD271 + Trunk Cell
Myocardial infarction
Célula tronco de medula óssea
Célula tronco CD271+
Infarto do miocárdio
topic Trunk cell of bone marrow
CD271 + Trunk Cell
Myocardial infarction
Célula tronco de medula óssea
Célula tronco CD271+
Infarto do miocárdio
description MSCs are a particularly promising bone marrow-derived cell for cardiac regenerative therapy because of their availability, immunologic properties, and record of safety and efficacy. Several studies have confirmed the specificity of CD271 on MSC isolated from bone marrow. This marker has been suggested as a versatile marker to selectively isolate multipotent MSC with both immunosuppressive and lymphohematopoietic engraftment-promoting properties. Moreover MSC are preferentially selected in the CD271+ fraction compared to the CD271− fraction. Objective: We hypothesized that CD271+ MSCs isolated from normal human BM will repair ischemic heart damage in a mouse myocardial infarction (MI) model. Methods: CD271+ cells were isolated and injected in NOD/SCID mice following induction of a myocardial infarction (MI) and the effects on cardiac function and hemodynamic were determined by echocardiography and PV loop, respectively. MI size was calculated by dividing the length of MI, defined as the region with >50% of myocardial wall thickness with collagen (blue) deposition with left ventricle length through MIQuant software and the human injected CD271+ cells were tracked by immunofluorescence using anti-human mitochondrial ribosomal protein L11. The data were performed using the SIGMAPLOT software and the values were expressed as mean±standard error of the mean (SEM). The level of statistical significance was set at p<0.05.Results: The CD271+ cells were capable to adhere at the plastic and showed a high capacity of expansion in vitro. Culture of the CD271+ cells under adherent conditions were not able to differentiate in osteo and adipogenic lineages. Animals treated with CD271+ cells had no significant improvement in heart function, however it demonstrated a tendency to preserve EF. Moreover, it was possible to track human cells at the infarcted zone in cell treated animals. Conclusion: We conclude that CD271 inhibited the differentiation of this cells into osteo and adipogenic lineages. These results indicate a role for CD271 in inhibiting the differentiation of MSC CD271+ and the intracardiac injected CD271+ MSC were able to home to infarcted zone after 8 weeks post-MI and demonstrate a trend to preserve EF.
publishDate 2018
dc.date.none.fl_str_mv 2018-03-29
2020-03-25T11:43:44Z
2020-03-25T11:43:44Z
dc.type.driver.fl_str_mv info:eu-repo/semantics/doctoralThesis
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
format doctoralThesis
status_str publishedVersion
dc.identifier.uri.fl_str_mv https://sucupira.capes.gov.br/sucupira/public/consultas/coleta/trabalhoConclusao/viewTrabalhoConclusao.jsf?popup=true&id_trabalho=7023888
ZUTTION, Marilia Sanches Santos Rizzo. Potencial terapêutico cardíaco das células tronco mesenquimais precursoras de medula óssea C D271+. 2018. 150 f. Tese (Doutorado em Biologia Estrutural e Funcional) - Escola Paulista de Medicina, Universidade Federal de S ão Paulo, São Paulo, 2018.
2018-0266.pdf
https://repositorio.unifesp.br/handle/11600/52334
url https://sucupira.capes.gov.br/sucupira/public/consultas/coleta/trabalhoConclusao/viewTrabalhoConclusao.jsf?popup=true&id_trabalho=7023888
https://repositorio.unifesp.br/handle/11600/52334
identifier_str_mv ZUTTION, Marilia Sanches Santos Rizzo. Potencial terapêutico cardíaco das células tronco mesenquimais precursoras de medula óssea C D271+. 2018. 150 f. Tese (Doutorado em Biologia Estrutural e Funcional) - Escola Paulista de Medicina, Universidade Federal de S ão Paulo, São Paulo, 2018.
2018-0266.pdf
dc.language.iso.fl_str_mv por
language por
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 90 f.
application/pdf
dc.coverage.none.fl_str_mv São Paulo
dc.publisher.none.fl_str_mv Universidade Federal de São Paulo (UNIFESP)
publisher.none.fl_str_mv Universidade Federal de São Paulo (UNIFESP)
dc.source.none.fl_str_mv reponame:Repositório Institucional da UNIFESP
instname:Universidade Federal de São Paulo (UNIFESP)
instacron:UNIFESP
instname_str Universidade Federal de São Paulo (UNIFESP)
instacron_str UNIFESP
institution UNIFESP
reponame_str Repositório Institucional da UNIFESP
collection Repositório Institucional da UNIFESP
repository.name.fl_str_mv Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)
repository.mail.fl_str_mv biblioteca.csp@unifesp.br
_version_ 1814268366073888768