Diferenciação hepatocítica de células-tronco mesenquimais da medula óssea humana
Autor(a) principal: | |
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Data de Publicação: | 2007 |
Outros Autores: | , , , |
Tipo de documento: | Artigo |
Idioma: | por |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://serv-bib.fcfar.unesp.br/seer/index.php/Cien_Farm/article/view/249 http://hdl.handle.net/11449/70132 |
Resumo: | Some recent articles have reported that mesenchymal stem cells (MSCs) can be induced to express hepatocyte markers by transplanting them into animal models of liver damage, or by in vitro culture with growth factors and cytokines. In this study, the aim is to evaluate the behavior of MSCs subjected to induction of hepatocyte differentiation. The MSCs were isolated from the bone marrow of 4 normal donors, characterized and subjected to both in vitro and in vivo induction of hepatocyte differentiation. The in vitro induced cells showed morphological changes, acquiring hepatocyte-like features. However, the immunophenotype of these cells was not modified. The induced cells exhibited no increase in albumin, cytokeratin 18 or cytokeratin 19 transcripts, when analyzed by real-time RT-PCR. The expression of albumin, cytokeratin 18 and alpha fetoprotein was also unchanged, according to immunofluorescence tests. In vivo, the MSC demonstrated a potential to migrate to damaged liver tissue in immunodeficient mice. Taken together, the results suggest that bone marrow MSCs are incapable of in vitro differentiation into hepatocytes by the approach used here, but are capable of homing to damaged hepatic tissue in vivo, suggesting a role for them in the repair of the liver. This contribution to tissue repair could be associated with a paracrine effect exerted by these cells. |
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Diferenciação hepatocítica de células-tronco mesenquimais da medula óssea humanaHepatocytic differentiation of human bone marrow mesenchymal stem cellsAlbuminCytokeratin 18Hepatocyte differentiationImmunodeficient miceLiver damageMesenchymal stem cellsalbuminalpha fetoproteincytokeratin 18animal cellanimal experimentanimal modelanimal tissuecell differentiationcell isolationcell migrationcell structurecontrolled studyhematopoietic stem cellhumanhuman cellimmunofluorescence testimmunophenotypingliver cellliver injurymesenchymal stem cellmousenonhumannormal humanparacrine signalingprotein expressionreal time polymerase chain reactionreverse transcription polymerase chain reactionSome recent articles have reported that mesenchymal stem cells (MSCs) can be induced to express hepatocyte markers by transplanting them into animal models of liver damage, or by in vitro culture with growth factors and cytokines. In this study, the aim is to evaluate the behavior of MSCs subjected to induction of hepatocyte differentiation. The MSCs were isolated from the bone marrow of 4 normal donors, characterized and subjected to both in vitro and in vivo induction of hepatocyte differentiation. The in vitro induced cells showed morphological changes, acquiring hepatocyte-like features. However, the immunophenotype of these cells was not modified. The induced cells exhibited no increase in albumin, cytokeratin 18 or cytokeratin 19 transcripts, when analyzed by real-time RT-PCR. The expression of albumin, cytokeratin 18 and alpha fetoprotein was also unchanged, according to immunofluorescence tests. In vivo, the MSC demonstrated a potential to migrate to damaged liver tissue in immunodeficient mice. Taken together, the results suggest that bone marrow MSCs are incapable of in vitro differentiation into hepatocytes by the approach used here, but are capable of homing to damaged hepatic tissue in vivo, suggesting a role for them in the repair of the liver. This contribution to tissue repair could be associated with a paracrine effect exerted by these cells.Algumas pesquisas realizadas recentemente relatam que as células-tronco mesenquimais (CTM) podem ser induzidas à aquisição de marcadores hepatocíticos pelo transplante em modelos animais de dano hepático, ou pelo cultivo in vitro com fatores de crescimento e citocinas. O presente estudo teve por objetivo avaliar o comportamento das CTM frente à indução da diferenciação hepatocítica. As CTM foram isoladas da medula óssea de quatro doadores saudáveis, caracterizadas e submetidas ao protocolo de indução à diferenciação hepatocítica in vitro e in vivo. As células induzidas in vitro apresentaram mudanças na sua morfologia, mostrando a morfologia semelhante à do hepatócito, porém, o perfil imunofenotípico não foi modificado. As células induzidas também não apresentaram o aumento dos transcritos de albumina, citoqueratina 18 e citoqueratina 19 quando analisadas por RT-PCR em tempo real, e não alteraram a expressão de albumina, citoqueratina 18 e alfa-fetoproteína como demonstrado por imunofluorescência. Quando analisadas in vivo, as CTM demonstraram o potencial migratório para o tecido hepático danificado de camundongos imunodeficientes. Em conjunto, os resultados sugerem que as CTM da medula óssea não são capazes de se diferenciar em hepatócitos quando estimuladas in vitro pela metodologia utilizada neste estudo, mas são capazes de migrar para o tecido hepático danificado in vivo, o que sugere o seu papel no reparo do fígado. A contribuição para o reparo pode estar associada com o efeito parácrino dessas células. Palavras-chave: célula-tronco mesenquimal; diferenciação hepatocítica; albumina; citoqueratina 18; dano hepático; camundongos imunodeficientesDepartemente de Análises Clínicas Faculdade de Ciências Farmacêuticas Universidade Estadual Paulista, UNESP, Araraquara, SPCentro Regional de Hemoterapia Hospital Das Clínicas Universidade de São Paulo, USP, Ribeirão Preto, SPDepartamento de Clínica Médica Faculdade de Medicina de Ribeirão Preto Universidade de São Paulo, USP, Ribeirão Preto, SPCentro Regional de Hemoterapia Hospital Das Clínicas Universidade de São Paulo, USP, Rua Tenente Catão Roxo 2501, CEP.: 14052-140 - Ribeirão Preto - SPDepartemente de Análises Clínicas Faculdade de Ciências Farmacêuticas Universidade Estadual Paulista, UNESP, Araraquara, SPUniversidade Estadual Paulista (Unesp)Universidade de São Paulo (USP)Penteado, F. C L [UNESP]Orellana, M. D.Fontes, A. M.Kashima, S.Covas, Dimas Tadeu2014-05-27T11:22:43Z2014-05-27T11:22:43Z2007-12-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article325-334application/pdfhttp://serv-bib.fcfar.unesp.br/seer/index.php/Cien_Farm/article/view/249Revista de Ciencias Farmaceuticas Basica e Aplicada, v. 28, n. 3, p. 325-334, 2007.1808-45322179-443Xhttp://hdl.handle.net/11449/701322-s2.0-500491188902-s2.0-50049118890.pdfScopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPporRevista de Ciências Farmacêuticas Básica e Aplicada0,131info:eu-repo/semantics/openAccess2024-06-21T15:18:33Zoai:repositorio.unesp.br:11449/70132Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-05T15:09:00.679065Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Diferenciação hepatocítica de células-tronco mesenquimais da medula óssea humana Hepatocytic differentiation of human bone marrow mesenchymal stem cells |
title |
Diferenciação hepatocítica de células-tronco mesenquimais da medula óssea humana |
spellingShingle |
Diferenciação hepatocítica de células-tronco mesenquimais da medula óssea humana Penteado, F. C L [UNESP] Albumin Cytokeratin 18 Hepatocyte differentiation Immunodeficient mice Liver damage Mesenchymal stem cells albumin alpha fetoprotein cytokeratin 18 animal cell animal experiment animal model animal tissue cell differentiation cell isolation cell migration cell structure controlled study hematopoietic stem cell human human cell immunofluorescence test immunophenotyping liver cell liver injury mesenchymal stem cell mouse nonhuman normal human paracrine signaling protein expression real time polymerase chain reaction reverse transcription polymerase chain reaction |
title_short |
Diferenciação hepatocítica de células-tronco mesenquimais da medula óssea humana |
title_full |
Diferenciação hepatocítica de células-tronco mesenquimais da medula óssea humana |
title_fullStr |
Diferenciação hepatocítica de células-tronco mesenquimais da medula óssea humana |
title_full_unstemmed |
Diferenciação hepatocítica de células-tronco mesenquimais da medula óssea humana |
title_sort |
Diferenciação hepatocítica de células-tronco mesenquimais da medula óssea humana |
author |
Penteado, F. C L [UNESP] |
author_facet |
Penteado, F. C L [UNESP] Orellana, M. D. Fontes, A. M. Kashima, S. Covas, Dimas Tadeu |
author_role |
author |
author2 |
Orellana, M. D. Fontes, A. M. Kashima, S. Covas, Dimas Tadeu |
author2_role |
author author author author |
dc.contributor.none.fl_str_mv |
Universidade Estadual Paulista (Unesp) Universidade de São Paulo (USP) |
dc.contributor.author.fl_str_mv |
Penteado, F. C L [UNESP] Orellana, M. D. Fontes, A. M. Kashima, S. Covas, Dimas Tadeu |
dc.subject.por.fl_str_mv |
Albumin Cytokeratin 18 Hepatocyte differentiation Immunodeficient mice Liver damage Mesenchymal stem cells albumin alpha fetoprotein cytokeratin 18 animal cell animal experiment animal model animal tissue cell differentiation cell isolation cell migration cell structure controlled study hematopoietic stem cell human human cell immunofluorescence test immunophenotyping liver cell liver injury mesenchymal stem cell mouse nonhuman normal human paracrine signaling protein expression real time polymerase chain reaction reverse transcription polymerase chain reaction |
topic |
Albumin Cytokeratin 18 Hepatocyte differentiation Immunodeficient mice Liver damage Mesenchymal stem cells albumin alpha fetoprotein cytokeratin 18 animal cell animal experiment animal model animal tissue cell differentiation cell isolation cell migration cell structure controlled study hematopoietic stem cell human human cell immunofluorescence test immunophenotyping liver cell liver injury mesenchymal stem cell mouse nonhuman normal human paracrine signaling protein expression real time polymerase chain reaction reverse transcription polymerase chain reaction |
description |
Some recent articles have reported that mesenchymal stem cells (MSCs) can be induced to express hepatocyte markers by transplanting them into animal models of liver damage, or by in vitro culture with growth factors and cytokines. In this study, the aim is to evaluate the behavior of MSCs subjected to induction of hepatocyte differentiation. The MSCs were isolated from the bone marrow of 4 normal donors, characterized and subjected to both in vitro and in vivo induction of hepatocyte differentiation. The in vitro induced cells showed morphological changes, acquiring hepatocyte-like features. However, the immunophenotype of these cells was not modified. The induced cells exhibited no increase in albumin, cytokeratin 18 or cytokeratin 19 transcripts, when analyzed by real-time RT-PCR. The expression of albumin, cytokeratin 18 and alpha fetoprotein was also unchanged, according to immunofluorescence tests. In vivo, the MSC demonstrated a potential to migrate to damaged liver tissue in immunodeficient mice. Taken together, the results suggest that bone marrow MSCs are incapable of in vitro differentiation into hepatocytes by the approach used here, but are capable of homing to damaged hepatic tissue in vivo, suggesting a role for them in the repair of the liver. This contribution to tissue repair could be associated with a paracrine effect exerted by these cells. |
publishDate |
2007 |
dc.date.none.fl_str_mv |
2007-12-01 2014-05-27T11:22:43Z 2014-05-27T11:22:43Z |
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://serv-bib.fcfar.unesp.br/seer/index.php/Cien_Farm/article/view/249 Revista de Ciencias Farmaceuticas Basica e Aplicada, v. 28, n. 3, p. 325-334, 2007. 1808-4532 2179-443X http://hdl.handle.net/11449/70132 2-s2.0-50049118890 2-s2.0-50049118890.pdf |
url |
http://serv-bib.fcfar.unesp.br/seer/index.php/Cien_Farm/article/view/249 http://hdl.handle.net/11449/70132 |
identifier_str_mv |
Revista de Ciencias Farmaceuticas Basica e Aplicada, v. 28, n. 3, p. 325-334, 2007. 1808-4532 2179-443X 2-s2.0-50049118890 2-s2.0-50049118890.pdf |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.relation.none.fl_str_mv |
Revista de Ciências Farmacêuticas Básica e Aplicada 0,131 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
325-334 application/pdf |
dc.source.none.fl_str_mv |
Scopus reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
institution |
UNESP |
reponame_str |
Repositório Institucional da UNESP |
collection |
Repositório Institucional da UNESP |
repository.name.fl_str_mv |
Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
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1808128467239174144 |