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Em colaboração com o grupo de investigação liderado por Lino Ferreira, do Biocant, temos desenvolvido trabalho de investigação translacional com o objectivo de promover uma melhor entrega de stem cells ao tecido isquémico num modelo animal de enfarte do miocárdio.

Several clinical trials are exploring the therapeutic effect of human CD34+ cells in ischemic diseases including myocardial infarction. Unfortunately, most of the cells die few days after delivery likely decreasing their therapeutic efficacy. Herein we show that lysophosphatidic acid (LPA)-treated human umbilical cord blood-derived CD34+ cells cultured under hypoxic and serum-deprived conditions show 2.2-fold (69.4±8.7% Annexin V-Propidium Iodide-) and 1.3-fold higher survival relatively to non-treated cells (30.6±19.6%) and prostaglandin E2-treated cells (54.6±11.6%), respectively. The pro-survival effect of LPA is concentration and time dependent which is mediated by the activation of peroxisome proliferator-activator receptor g (PPARg) 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 undifferentiating state of CD34+ cells, and enhances IL-8, IL-6 and G-SCF secretion during the first 12 h as 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 non-treated cells (+9.5 versus -1.1, normalized by day 1). 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.