Lysophosphatidic acid enhances survival of human CD34(+) cells in ischemic conditions
Autor(a) principal: | |
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Data de Publicação: | 2015 |
Outros Autores: | , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10400.4/2082 |
Resumo: | Several clinical trials are exploring therapeutic effect of human CD34(+) cells in ischemic diseases, including myocardial infarction. Unfortunately, most of the cells die few days after delivery. Herein we show that lysophosphatidic acid (LPA)-treated human umbilical cord blood-derived CD34(+) cells cultured under hypoxic and serum-deprived conditions present 2.2-fold and 1.3-fold higher survival relatively to non-treated cells and prostaglandin E2-treated cells, respectively. The pro-survival effect of LPA is concentration- and time-dependent and it is mediated by the activation of peroxisome proliferator-activator receptor γ (PPARγ) and downstream, by the activation of pro-survival ERK and Akt signaling pathways and the inhibition of mitochondrial apoptotic pathway. In hypoxia and serum-deprived culture conditions, LPA induces CD34(+) cell proliferation without maintaining the their undifferentiating state, and enhances IL-8, IL-6 and G-CSF secretion during the first 12 h compared to non-treated cells. LPA-treated CD34(+) cells delivered in fibrin gels have enhanced survival and improved cardiac fractional shortening at 2 weeks on rat infarcted hearts as compared to hearts treated with placebo. We have developed a new platform to enhance the survival of CD34(+) cells using a natural and cost-effective ligand and demonstrated its utility in the preservation of the functionality of the heart after infarction. |
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Lysophosphatidic acid enhances survival of human CD34(+) cells in ischemic conditionsAntigénio CD34Sobrevivência CelularCélulas-Tronco HematopoéticasIsquemiaLisofosfolipídeosEnfarte do MiocárdioSeveral clinical trials are exploring therapeutic effect of human CD34(+) cells in ischemic diseases, including myocardial infarction. Unfortunately, most of the cells die few days after delivery. Herein we show that lysophosphatidic acid (LPA)-treated human umbilical cord blood-derived CD34(+) cells cultured under hypoxic and serum-deprived conditions present 2.2-fold and 1.3-fold higher survival relatively to non-treated cells and prostaglandin E2-treated cells, respectively. The pro-survival effect of LPA is concentration- and time-dependent and it is mediated by the activation of peroxisome proliferator-activator receptor γ (PPARγ) and downstream, by the activation of pro-survival ERK and Akt signaling pathways and the inhibition of mitochondrial apoptotic pathway. In hypoxia and serum-deprived culture conditions, LPA induces CD34(+) cell proliferation without maintaining the their undifferentiating state, and enhances IL-8, IL-6 and G-CSF secretion during the first 12 h compared to non-treated cells. LPA-treated CD34(+) cells delivered in fibrin gels have enhanced survival and improved cardiac fractional shortening at 2 weeks on rat infarcted hearts as compared to hearts treated with placebo. We have developed a new platform to enhance the survival of CD34(+) cells using a natural and cost-effective ligand and demonstrated its utility in the preservation of the functionality of the heart after infarction.RIHUCKostic, IFidalgo-Carvalho, IAday, SVazão, HCarvalheiro, TGrãos, MDuarte, ACardoso, CGonçalves, LCarvalho, LPaiva, AFerreira, L2017-08-29T15:12:26Z2015-11-102015-11-10T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.4/2082engSci Rep. 2015 Nov 10;5:16406.10.1038/srep16406info: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:RCAAP2023-07-11T14:23:23Zoai:rihuc.huc.min-saude.pt:10400.4/2082Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T18:04:33.244057Repositório 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 |
Lysophosphatidic acid enhances survival of human CD34(+) cells in ischemic conditions |
title |
Lysophosphatidic acid enhances survival of human CD34(+) cells in ischemic conditions |
spellingShingle |
Lysophosphatidic acid enhances survival of human CD34(+) cells in ischemic conditions Kostic, I Antigénio CD34 Sobrevivência Celular Células-Tronco Hematopoéticas Isquemia Lisofosfolipídeos Enfarte do Miocárdio |
title_short |
Lysophosphatidic acid enhances survival of human CD34(+) cells in ischemic conditions |
title_full |
Lysophosphatidic acid enhances survival of human CD34(+) cells in ischemic conditions |
title_fullStr |
Lysophosphatidic acid enhances survival of human CD34(+) cells in ischemic conditions |
title_full_unstemmed |
Lysophosphatidic acid enhances survival of human CD34(+) cells in ischemic conditions |
title_sort |
Lysophosphatidic acid enhances survival of human CD34(+) cells in ischemic conditions |
author |
Kostic, I |
author_facet |
Kostic, I Fidalgo-Carvalho, I Aday, S Vazão, H Carvalheiro, T Grãos, M Duarte, A Cardoso, C Gonçalves, L Carvalho, L Paiva, A Ferreira, L |
author_role |
author |
author2 |
Fidalgo-Carvalho, I Aday, S Vazão, H Carvalheiro, T Grãos, M Duarte, A Cardoso, C Gonçalves, L Carvalho, L Paiva, A Ferreira, L |
author2_role |
author author author author author author author author author author author |
dc.contributor.none.fl_str_mv |
RIHUC |
dc.contributor.author.fl_str_mv |
Kostic, I Fidalgo-Carvalho, I Aday, S Vazão, H Carvalheiro, T Grãos, M Duarte, A Cardoso, C Gonçalves, L Carvalho, L Paiva, A Ferreira, L |
dc.subject.por.fl_str_mv |
Antigénio CD34 Sobrevivência Celular Células-Tronco Hematopoéticas Isquemia Lisofosfolipídeos Enfarte do Miocárdio |
topic |
Antigénio CD34 Sobrevivência Celular Células-Tronco Hematopoéticas Isquemia Lisofosfolipídeos Enfarte do Miocárdio |
description |
Several clinical trials are exploring therapeutic effect of human CD34(+) cells in ischemic diseases, including myocardial infarction. Unfortunately, most of the cells die few days after delivery. Herein we show that lysophosphatidic acid (LPA)-treated human umbilical cord blood-derived CD34(+) cells cultured under hypoxic and serum-deprived conditions present 2.2-fold and 1.3-fold higher survival relatively to non-treated cells and prostaglandin E2-treated cells, respectively. The pro-survival effect of LPA is concentration- and time-dependent and it is mediated by the activation of peroxisome proliferator-activator receptor γ (PPARγ) and downstream, by the activation of pro-survival ERK and Akt signaling pathways and the inhibition of mitochondrial apoptotic pathway. In hypoxia and serum-deprived culture conditions, LPA induces CD34(+) cell proliferation without maintaining the their undifferentiating state, and enhances IL-8, IL-6 and G-CSF secretion during the first 12 h compared to non-treated cells. LPA-treated CD34(+) cells delivered in fibrin gels have enhanced survival and improved cardiac fractional shortening at 2 weeks on rat infarcted hearts as compared to hearts treated with placebo. We have developed a new platform to enhance the survival of CD34(+) cells using a natural and cost-effective ligand and demonstrated its utility in the preservation of the functionality of the heart after infarction. |
publishDate |
2015 |
dc.date.none.fl_str_mv |
2015-11-10 2015-11-10T00:00:00Z 2017-08-29T15:12:26Z |
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/10400.4/2082 |
url |
http://hdl.handle.net/10400.4/2082 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Sci Rep. 2015 Nov 10;5:16406. 10.1038/srep16406 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
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 |
instname_str |
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) |
collection |
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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