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Unfortunately, most of the cells die few days after delivery. Herein we show that lysophosphatidic acid (LPA)-treated human umbilical cord blood-derived CD34<jats:sup>+<\/jats:sup> 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<jats:sub>2<\/jats:sub>-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 \u03b3 (PPAR\u03b3) 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<jats:sup>+<\/jats:sup> cell proliferation without maintaining the their undifferentiating state and enhances IL-8, IL-6 and G-CSF secretion during the first 12\u2009h compared to non-treated cells. LPA-treated CD34<jats:sup>+<\/jats:sup> 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<jats:sup>+<\/jats:sup> cells using a natural and cost-effective ligand and demonstrated its utility in the preservation of the functionality of the heart after infarction.<\/jats:p>","DOI":"10.1038\/srep16406","type":"journal-article","created":{"date-parts":[[2015,11,10]],"date-time":"2015-11-10T10:11:20Z","timestamp":1447150280000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Lysophosphatidic acid enhances survival of human CD34+ cells in ischemic conditions"],"prefix":"10.1038","volume":"5","author":[{"given":"Ivana","family":"Kostic","sequence":"first","affiliation":[]},{"given":"Isabel","family":"Fidalgo-Carvalho","sequence":"additional","affiliation":[]},{"given":"Sezin","family":"Aday","sequence":"additional","affiliation":[]},{"given":"Helena","family":"Vaz\u00e3o","sequence":"additional","affiliation":[]},{"given":"Tiago","family":"Carvalheiro","sequence":"additional","affiliation":[]},{"given":"M\u00e1rio","family":"Gr\u00e3os","sequence":"additional","affiliation":[]},{"given":"Ant\u00f3nio","family":"Duarte","sequence":"additional","affiliation":[]},{"given":"Carla","family":"Cardoso","sequence":"additional","affiliation":[]},{"given":"Lino","family":"Gon\u00e7alves","sequence":"additional","affiliation":[]},{"given":"Lina","family":"Carvalho","sequence":"additional","affiliation":[]},{"given":"Artur","family":"Paiva","sequence":"additional","affiliation":[]},{"given":"Lino","family":"Ferreira","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2015,11,10]]},"reference":[{"key":"BFsrep16406_CR1","doi-asserted-by":"publisher","first-page":"1471","DOI":"10.1161\/CIRCRESAHA.108.175174","volume":"102","author":"MS Penn","year":"2008","unstructured":"Penn, M. 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