Publications
Detailed Information
Mechanisms of paracrine cardioprotection by cord blood mesenchymal stromal cells
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Bader, Andreas Matthaeus | - |
dc.contributor.author | Brodarac, Andreja | - |
dc.contributor.author | Klose, Kristin | - |
dc.contributor.author | Bieback, Karen | - |
dc.contributor.author | Choi, Yeong-Hoon | - |
dc.contributor.author | Kurtz, Andreas | - |
dc.contributor.author | Stamm, Christof | - |
dc.date.accessioned | 2023-05-10T01:25:07Z | - |
dc.date.available | 2023-05-10T01:25:07Z | - |
dc.date.created | 2023-03-29 | - |
dc.date.issued | 2014-06 | - |
dc.identifier.citation | European Journal of Cardio-thoracic Surgery, Vol.45 No.6, pp.983-992 | - |
dc.identifier.issn | 1010-7940 | - |
dc.identifier.uri | https://hdl.handle.net/10371/192310 | - |
dc.description.abstract | OBJECTIVES: Among the mechanisms by which somatic stem cells may improve left ventricular function in ischaemic heart disease are pro-survival stimuli mediated by secreted factors. This phenomenon is frequently referred to, but remains poorly understood. We therefore investigated the non-regenerative cardioprotective effects of cord blood mesenchymal stromal cells (CBMSCs) in vitro and sought to identify relevant intracellular signalling pathways. METHODS: Conditioned medium from CBMSCs and fibroblasts was prepared, and secreted factors were analysed by Luminex. ® immunobead assay. Murine cardiomyocyte-derived HL-1 cells were subjected to simulated ischaemia by glucose and serum deprivation and hypoxia in CBMSC-conditioned or cell-free control medium or in medium conditioned by foreskin fibroblasts. The proportions of vital, apoptotic and necrotic cells (poly-caspase activity, annexin V and ethidium homodimer-III staining) were quantified using a high-content imaging system. Metabolic activity and proliferation rate were determined via 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium and 5-bromo-2-deoxyuridine assays. Phosphorylation of Akt, extracellular-signal-regulated kinase (ERK)1/2, signal transducer and activator of transcription 3 (STAT3) and glycogen synthase kinase 3β was determined by western blot, and experiments were repeated in the presence of specific small-molecule inhibitors (Wortmannin, UO126 and Stattic). RESULTS: CBMSC medium reduced the proportion of dead HL-1 cardiomyocytes from 39 ± 3 to 28 ± 1% (P < 0.05) and the rate of late apoptotic cells to 68 ± 2% of that in control medium (P < 0.001). Metabolic activity was increased by 12 ± 1% compared with control (P < 0.05), while in fibroblast medium it was not (5 ± 2%, P = 1). This was associated with increased phosphorylation of Akt (2-fold, P < 0.05), ERK1/2 (3-fold, P < 0.01) and STAT3 (12-fold, P < 0.001). Combined blocking of the phosphatidylinositol-4,5-bisphosphate 3-kinase/Akt and mitogen-activated protein kinase/ERK signalling abolished the protective CBMSC effect, while blocking the pathways individually had no effect. Inhibition of STAT3 phosphorylation drastically lowered HL-1 cell viability in control medium, but not in medium conditioned by CBMSCs. CONCLUSIONS: The factors released by CBMSCs protect cardiomyocyte-like HL-1 cells from simulated ischaemia more than those released from fibroblasts. While CBMSC-triggered Akt and ERK1/2 activation provides protection in a compensatory manner, STAT3 is crucial for cardiomyocyte survival in ischaemia, but is not a key mediator of cytoprotective stem cell actions. © The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved. | - |
dc.language | 영어 | - |
dc.publisher | Elsevier BV | - |
dc.title | Mechanisms of paracrine cardioprotection by cord blood mesenchymal stromal cells | - |
dc.type | Article | - |
dc.identifier.doi | 10.1093/ejcts/ezt576 | - |
dc.citation.journaltitle | European Journal of Cardio-thoracic Surgery | - |
dc.identifier.wosid | 000336997100014 | - |
dc.identifier.scopusid | 2-s2.0-84900541575 | - |
dc.citation.endpage | 992 | - |
dc.citation.number | 6 | - |
dc.citation.startpage | 983 | - |
dc.citation.volume | 45 | - |
dc.description.isOpenAccess | Y | - |
dc.contributor.affiliatedAuthor | Kurtz, Andreas | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.subject.keywordPlus | BONE-MARROW-CELLS | - |
dc.subject.keywordPlus | STEM-CELLS | - |
dc.subject.keywordPlus | MYOCARDIAL-INFARCTION | - |
dc.subject.keywordPlus | IN-VITRO | - |
dc.subject.keywordPlus | SURVIVAL | - |
dc.subject.keywordPlus | REPERFUSION | - |
dc.subject.keywordPlus | ACTIVATION | - |
dc.subject.keywordPlus | THERAPY | - |
dc.subject.keywordPlus | STAT3 | - |
dc.subject.keywordAuthor | Cardiomyocyte | - |
dc.subject.keywordAuthor | Cell therapy | - |
dc.subject.keywordAuthor | Cord blood | - |
dc.subject.keywordAuthor | Ischaemia | - |
dc.subject.keywordAuthor | Stem cell | - |
- Appears in Collections:
- Files in This Item:
- There are no files associated with this item.
Item View & Download Count
Items in S-Space are protected by copyright, with all rights reserved, unless otherwise indicated.