Journal
SCIENTIFIC REPORTS
Volume 5, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/srep16406
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Funding
- Fundacao para a Ciencia e a Tecnologia [PTDC/BIM-MED/1118/2012, SFRH/BD/51114/2010]
- Crioestaminal [CENTRO-01-0202-FEDER-005476]
- COMPETE funding (Project Stem cell based platforms for Regenerative and Therapeutic Medicine) [Centro-07-ST24-FEDER-002008]
- Fundação para a Ciência e a Tecnologia [PTDC/BIM-MED/1118/2012, SFRH/BD/51114/2010] Funding Source: FCT
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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 E-2-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 gamma (PPAR gamma) 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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