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- Title
Lysophosphatidic acid enhances survival of human CD34<sup>+</sup> 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
- 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.
- Subjects
LYSOPHOSPHOLIPIDS; PEROXISOME proliferator-activated receptors; CORONARY heart disease prevention; CELL communication; MEMBRANE glycoproteins
- Publication
Scientific Reports, 2015, p16406
- ISSN
2045-2322
- Publication type
Article
- DOI
10.1038/srep16406