Publication
Lysophosphatidic acid enhances survival of human CD34(+) cells in ischemic conditions
| dc.contributor.author | Kostic, I | |
| dc.contributor.author | Fidalgo-Carvalho, I | |
| dc.contributor.author | Aday, S | |
| dc.contributor.author | Vazão, H | |
| dc.contributor.author | Carvalheiro, T | |
| dc.contributor.author | Grãos, M | |
| dc.contributor.author | Duarte, A | |
| dc.contributor.author | Cardoso, C | |
| dc.contributor.author | Gonçalves, L | |
| dc.contributor.author | Carvalho, L | |
| dc.contributor.author | Paiva, A | |
| dc.contributor.author | Ferreira, L | |
| dc.date.accessioned | 2017-08-29T15:12:26Z | |
| dc.date.available | 2017-08-29T15:12:26Z | |
| dc.date.issued | 2015-11-10 | |
| dc.description.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. | pt_PT |
| dc.description.version | info:eu-repo/semantics/publishedVersion | pt_PT |
| dc.identifier.citation | Sci Rep. 2015 Nov 10;5:16406. | pt_PT |
| dc.identifier.doi | 10.1038/srep16406 | pt_PT |
| dc.identifier.uri | http://hdl.handle.net/10400.4/2082 | |
| dc.language.iso | eng | pt_PT |
| dc.peerreviewed | yes | pt_PT |
| dc.subject | Antigénio CD34 | pt_PT |
| dc.subject | Sobrevivência Celular | pt_PT |
| dc.subject | Células-Tronco Hematopoéticas | pt_PT |
| dc.subject | Isquemia | pt_PT |
| dc.subject | Lisofosfolipídeos | pt_PT |
| dc.subject | Enfarte do Miocárdio | pt_PT |
| dc.title | Lysophosphatidic acid enhances survival of human CD34(+) cells in ischemic conditions | pt_PT |
| dc.type | journal article | |
| dspace.entity.type | Publication | |
| oaire.citation.issue | 1 | pt_PT |
| oaire.citation.startPage | 16406 | pt_PT |
| oaire.citation.volume | 5 | pt_PT |
| rcaap.rights | openAccess | pt_PT |
| rcaap.type | article | pt_PT |