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http://hdl.handle.net/10362/96256
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Campo DC | Valor | Idioma |
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dc.contributor.author | Sebastiao, Maria J. | - |
dc.contributor.author | Serra, Margarida | - |
dc.contributor.author | Pereira, Rute | - |
dc.contributor.author | Palacios, Itziar | - |
dc.contributor.author | Gomes-Alves, Patricia | - |
dc.contributor.author | Alves, Paula M. | - |
dc.date.accessioned | 2020-04-15T22:37:16Z | - |
dc.date.available | 2020-04-15T22:37:16Z | - |
dc.date.issued | 2019-03-07 | - |
dc.identifier.issn | 1757-6512 | - |
dc.identifier.other | PURE: 17681848 | - |
dc.identifier.other | PURE UUID: 69706840-de27-4c38-9984-88ad8929044e | - |
dc.identifier.other | WOS: 000460811700003 | - |
dc.identifier.other | Scopus: 85062601493 | - |
dc.identifier.other | PubMed: 30845956 | - |
dc.identifier.uri | http://hdl.handle.net/10362/96256 | - |
dc.description.abstract | Background: 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.iso | eng | - |
dc.rights | openAccess | - |
dc.subject | Cardiac progenitor cells, myocardial infarction | - |
dc.subject | Ischemia-reperfusion injury | - |
dc.subject | Myocardial ischemia reperfusion injury | - |
dc.subject | Proteomics | - |
dc.subject | Medicine (miscellaneous) | - |
dc.subject | Molecular Medicine | - |
dc.subject | Biochemistry, Genetics and Molecular Biology (miscellaneous) | - |
dc.subject | Cell Biology | - |
dc.title | Human cardiac progenitor cell activation and regeneration mechanisms | - |
dc.type | article | - |
degois.publication.issue | 1 | - |
degois.publication.title | STEM CELL RESEARCH THERAPY | - |
degois.publication.volume | 10 | - |
dc.peerreviewed | yes | - |
dc.identifier.doi | https://doi.org/10.1186/s13287-019-1174-4 | - |
dc.description.version | published | - |
dc.title.subtitle | exploring a novel myocardial ischemia/reperfusion in vitro model | - |
dc.contributor.institution | Instituto de Tecnologia Química e Biológica António Xavier (ITQB) | - |
Aparece nas colecções: | Home collection (ITQB) |
Ficheiros deste registo:
Ficheiro | Descrição | Tamanho | Formato | |
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Human_cardiac_progenitor_cell_activation.pdf | 4,6 MB | Adobe PDF | Ver/Abrir |
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