Diferenciação hepatocítica de células-tronco mesenquimais da medula óssea humana

Detalhes bibliográficos
Autor(a) principal: Penteado, F. C L [UNESP]
Data de Publicação: 2007
Outros Autores: Orellana, M. D., Fontes, A. M., Kashima, S., Covas, Dimas Tadeu
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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spelling 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
_version_ 1808128467239174144