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https://hdl.handle.net/10316/109318
Título: | Lysophosphatidic acid enhances survival of human CD34(+) cells in ischemic conditions | Autor: | Kostic, Ivana Fidalgo-Carvalho, Isabel Aday, Sezin Vazão, Helena Carvalheiro, Tiago Grãos, Mário Duarte, António Cardoso, Carla Gonçalves, Lino Carvalho, Lina Paiva, Artur Ferreira, Lino |
Data: | 10-Nov-2015 | Editora: | Springer Nature | Projeto: | PTDC/BIM-MED/1118/2012 SFRH/BD/51114/2010 Crioestaminal (Project no. CENTRO-01-0202-FEDER-005476 “INJECTCORD) COMPETE funding (Project “Stem cell based platforms for Regenerative and Therapeutic Medicine”, Centro-07-ST24-FEDER-002008) |
Título da revista, periódico, livro ou evento: | Scientific Reports | Volume: | 5 | Número: | 1 | 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. | URI: | https://hdl.handle.net/10316/109318 | ISSN: | 2045-2322 | DOI: | 10.1038/srep16406 | Direitos: | openAccess |
Aparece nas coleções: | FMUC Medicina - Artigos em Revistas Internacionais I&D CNC - Artigos em Revistas Internacionais |
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Ficheiro | Descrição | Tamanho | Formato | |
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Lysophosphatidic-acid-enhances-survival-of-human-CD34supsup-cells-in-ischemic-conditionsScientific-Reports.pdf | 7 MB | Adobe PDF | Ver/Abrir |
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