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Title: Lysophosphatidic acid enhances survival of human CD34(+) cells in ischemic conditions
Authors: 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 
Issue Date: 10-Nov-2015
Publisher: Springer Nature
Project: PTDC/BIM-MED/1118/2012 
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) 
Serial title, monograph or event: Scientific Reports
Volume: 5
Issue: 1
Abstract: 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.
ISSN: 2045-2322
DOI: 10.1038/srep16406
Rights: openAccess
Appears in Collections:FMUC Medicina - Artigos em Revistas Internacionais
I&D CNC - Artigos em Revistas Internacionais

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