Utilize este identificador para referenciar este registo: http://hdl.handle.net/10362/96256
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Campo DCValorIdioma
dc.contributor.authorSebastiao, Maria J.-
dc.contributor.authorSerra, Margarida-
dc.contributor.authorPereira, Rute-
dc.contributor.authorPalacios, Itziar-
dc.contributor.authorGomes-Alves, Patricia-
dc.contributor.authorAlves, Paula M.-
dc.date.accessioned2020-04-15T22:37:16Z-
dc.date.available2020-04-15T22:37:16Z-
dc.date.issued2019-03-07-
dc.identifier.issn1757-6512-
dc.identifier.otherPURE: 17681848-
dc.identifier.otherPURE UUID: 69706840-de27-4c38-9984-88ad8929044e-
dc.identifier.otherWOS: 000460811700003-
dc.identifier.otherScopus: 85062601493-
dc.identifier.otherPubMed: 30845956-
dc.identifier.urihttp://hdl.handle.net/10362/96256-
dc.description.abstractBackground: Numerous studies from different labs around the world report human cardiac progenitor cells (hCPCs) as having a role in myocardial repair upon ischemia/reperfusion (I/R) injury, mainly through auto/paracrine signaling. Even though these cell populations are already being investigated in cell transplantation-based clinical trials, the mechanisms underlying their response are still poorly understood. Methods: To further investigate hCPC regenerative process, we established the first in vitro human heterotypic model of myocardial I/R injury using hCPCs and human-induced pluripotent cell-derived cardiomyocytes (hiPSC-CMs). The co-culture model was established using transwell inserts and evaluated in both ischemia and reperfusion phases regarding secretion of key cytokines, hiPSC-CM viability, and hCPC proliferation. hCPC proteome in response to I/R was further characterized using advanced liquid chromatography mass spectrometry tools. Results: This model recapitulates hallmarks of I/R, namely hiPSC-CM death upon insult, protective effect of hCPCs on hiPSC-CM viability (37.6% higher vs hiPSC-CM mono-culture), and hCPC proliferation (approximately threefold increase vs hCPCs mono-culture), emphasizing the importance of paracrine communication between these two populations. In particular, in co-culture supernatant upon injury, we report higher angiogenic functionality as well as a significant increase in the CXCL6 secretion rate, suggesting an important role of this chemokine in myocardial regeneration. hCPC whole proteome analysis allowed us to propose new pathways in the hCPC-mediated regenerative process, including cell cycle regulation, proliferation through EGF signaling, and reactive oxygen species detoxification. Conclusion: This work contributes with new insights into hCPC biology in response to I/R, and the model established constitutes an important tool to study the molecular mechanisms involved in the myocardial regenerative process.en
dc.language.isoeng-
dc.rightsopenAccess-
dc.subjectCardiac progenitor cells, myocardial infarction-
dc.subjectIschemia-reperfusion injury-
dc.subjectMyocardial ischemia reperfusion injury-
dc.subjectProteomics-
dc.subjectMedicine (miscellaneous)-
dc.subjectMolecular Medicine-
dc.subjectBiochemistry, Genetics and Molecular Biology (miscellaneous)-
dc.subjectCell Biology-
dc.titleHuman cardiac progenitor cell activation and regeneration mechanisms-
dc.typearticle-
degois.publication.issue1-
degois.publication.titleSTEM CELL RESEARCH THERAPY-
degois.publication.volume10-
dc.peerreviewedyes-
dc.identifier.doihttps://doi.org/10.1186/s13287-019-1174-4-
dc.description.versionpublished-
dc.title.subtitleexploring a novel myocardial ischemia/reperfusion in vitro model-
dc.contributor.institutionInstituto de Tecnologia Química e Biológica António Xavier (ITQB)-
Aparece nas colecções:Home collection (ITQB)

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