Human-umbilical cord matrix mesenchymal cells improved left ventricular contractility independently of infarct size in swine myocardial infarction with reperfusion
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2023 |
| Outros Autores: | , , , , , , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
| Texto Completo: | http://hdl.handle.net/10362/154562 |
Resumo: | Funding Information: This work was funded by: i) national funds through FCT - Portuguese Foundation for Science and Technology, under the scope of the Cardiovascular R&D Center - UnIC (UIDB/00051/2020 and UIDP/00051/2020); ii) “la Caixa” Banking Foundation and FCT under the project code LCF/PR/HP17/52190002”; iii) the QREN project 2013/30196; and iv) the European Structural and Investment Funds (ESIF), under the Lisbon Portugal Regional Operational Program and National Funds through FCT [POCI-01-0145-FEDER-030985]. RNG and TLL were funded by the FCT individual fellowships [SFRH/BD/144490/2019] and [PD/BD/127997/2016], respectively. Funding sources had no interference in the design of the study, study governance, data collection and analysis, nor in manuscript writing or its scientific and intellectual content. Publisher Copyright: 2023 Raposo, Cerqueira, Leite, Moreira-Costa, Laundos, Miranda, Mendes-Ferreira, Coelho, Gomes, Pinto-do-Ó, Nascimento, Lourenço, Cardim and Leite-Moreira. |
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Human-umbilical cord matrix mesenchymal cells improved left ventricular contractility independently of infarct size in swine myocardial infarction with reperfusionmesenchymal cellsMSCmyocardial infarctionreperfusionumbilical-cordCardiology and Cardiovascular MedicineFunding Information: This work was funded by: i) national funds through FCT - Portuguese Foundation for Science and Technology, under the scope of the Cardiovascular R&D Center - UnIC (UIDB/00051/2020 and UIDP/00051/2020); ii) “la Caixa” Banking Foundation and FCT under the project code LCF/PR/HP17/52190002”; iii) the QREN project 2013/30196; and iv) the European Structural and Investment Funds (ESIF), under the Lisbon Portugal Regional Operational Program and National Funds through FCT [POCI-01-0145-FEDER-030985]. RNG and TLL were funded by the FCT individual fellowships [SFRH/BD/144490/2019] and [PD/BD/127997/2016], respectively. Funding sources had no interference in the design of the study, study governance, data collection and analysis, nor in manuscript writing or its scientific and intellectual content. Publisher Copyright: 2023 Raposo, Cerqueira, Leite, Moreira-Costa, Laundos, Miranda, Mendes-Ferreira, Coelho, Gomes, Pinto-do-Ó, Nascimento, Lourenço, Cardim and Leite-Moreira.Background: Human umbilical cord matrix-mesenchymal stromal cells (hUCM-MSC) have demonstrated beneficial effects in experimental acute myocardial infarction (AMI). Reperfusion injury hampers myocardial recovery in a clinical setting and its management is an unmet need. We investigated the efficacy of intracoronary (IC) delivery of xenogeneic hUCM-MSC as reperfusion-adjuvant therapy in a translational model of AMI in swine. Methods: In a placebo-controlled trial, pot-belied pigs were randomly assigned to a sham-control group (vehicle-injection; n = 8), AMI + vehicle (n = 12) or AMI + IC-injection (n = 11) of 5 × 105 hUCM-MSC/Kg, within 30 min of reperfusion. AMI was created percutaneously by balloon occlusion of the mid-LAD. Left-ventricular function was blindly evaluated at 8-weeks by invasive pressure-volume loop analysis (primary endpoint). Mechanistic readouts included histology, strength-length relationship in skinned cardiomyocytes and gene expression analysis by RNA-sequencing. Results: As compared to vehicle, hUCM-MSC enhanced systolic function as shown by higher ejection fraction (65 ± 6% vs. 43 ± 4%; p = 0.0048), cardiac index (4.1 ± 0.4 vs. 3.1 ± 0.2 L/min/m2; p = 0.0378), preload recruitable stroke work (75 ± 13 vs. 36 ± 4 mmHg; p = 0.0256) and end-systolic elastance (2.8 ± 0.7 vs. 2.1 ± 0.4 mmHg*m2/ml; p = 0.0663). Infarct size was non-significantly lower in cell-treated animals (13.7 ± 2.2% vs. 15.9 ± 2.7%; Δ = −2.2%; p = 0.23), as was interstitial fibrosis and cardiomyocyte hypertrophy in the remote myocardium. Sarcomere active tension improved, and genes related to extracellular matrix remodelling (including MMP9, TIMP1 and PAI1), collagen fibril organization and glycosaminoglycan biosynthesis were downregulated in animals treated with hUCM-MSC. Conclusion: Intracoronary transfer of xenogeneic hUCM-MSC shortly after reperfusion improved left-ventricular systolic function, which could not be explained by the observed extent of infarct size reduction alone. Combined contributions of favourable modification of myocardial interstitial fibrosis, matrix remodelling and enhanced cardiomyocyte contractility in the remote myocardium may provide mechanistic insight for the biological effect.NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)RUNRaposo, LuísCerqueira, Rui J.Leite, SaraMoreira-Costa, LilianaLaundos, Tiago L.Miranda, Joana O.Mendes-Ferreira, PedroCoelho, João AlmeidaGomes, Rita N.Pinto-do-Ó, PerpétuaNascimento, Diana S.Lourenço, André P.Cardim, NunoLeite-Moreira, Adelino2023-06-28T22:18:24Z2023-062023-06-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10362/154562eng2297-055XPURE: 64789697https://doi.org/10.3389/fcvm.2023.1186574info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-03-11T05:36:59Zoai:run.unl.pt:10362/154562Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:55:40.256327Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
| dc.title.none.fl_str_mv |
Human-umbilical cord matrix mesenchymal cells improved left ventricular contractility independently of infarct size in swine myocardial infarction with reperfusion |
| title |
Human-umbilical cord matrix mesenchymal cells improved left ventricular contractility independently of infarct size in swine myocardial infarction with reperfusion |
| spellingShingle |
Human-umbilical cord matrix mesenchymal cells improved left ventricular contractility independently of infarct size in swine myocardial infarction with reperfusion Raposo, Luís mesenchymal cells MSC myocardial infarction reperfusion umbilical-cord Cardiology and Cardiovascular Medicine |
| title_short |
Human-umbilical cord matrix mesenchymal cells improved left ventricular contractility independently of infarct size in swine myocardial infarction with reperfusion |
| title_full |
Human-umbilical cord matrix mesenchymal cells improved left ventricular contractility independently of infarct size in swine myocardial infarction with reperfusion |
| title_fullStr |
Human-umbilical cord matrix mesenchymal cells improved left ventricular contractility independently of infarct size in swine myocardial infarction with reperfusion |
| title_full_unstemmed |
Human-umbilical cord matrix mesenchymal cells improved left ventricular contractility independently of infarct size in swine myocardial infarction with reperfusion |
| title_sort |
Human-umbilical cord matrix mesenchymal cells improved left ventricular contractility independently of infarct size in swine myocardial infarction with reperfusion |
| author |
Raposo, Luís |
| author_facet |
Raposo, Luís Cerqueira, Rui J. Leite, Sara Moreira-Costa, Liliana Laundos, Tiago L. Miranda, Joana O. Mendes-Ferreira, Pedro Coelho, João Almeida Gomes, Rita N. Pinto-do-Ó, Perpétua Nascimento, Diana S. Lourenço, André P. Cardim, Nuno Leite-Moreira, Adelino |
| author_role |
author |
| author2 |
Cerqueira, Rui J. Leite, Sara Moreira-Costa, Liliana Laundos, Tiago L. Miranda, Joana O. Mendes-Ferreira, Pedro Coelho, João Almeida Gomes, Rita N. Pinto-do-Ó, Perpétua Nascimento, Diana S. Lourenço, André P. Cardim, Nuno Leite-Moreira, Adelino |
| author2_role |
author author author author author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM) RUN |
| dc.contributor.author.fl_str_mv |
Raposo, Luís Cerqueira, Rui J. Leite, Sara Moreira-Costa, Liliana Laundos, Tiago L. Miranda, Joana O. Mendes-Ferreira, Pedro Coelho, João Almeida Gomes, Rita N. Pinto-do-Ó, Perpétua Nascimento, Diana S. Lourenço, André P. Cardim, Nuno Leite-Moreira, Adelino |
| dc.subject.por.fl_str_mv |
mesenchymal cells MSC myocardial infarction reperfusion umbilical-cord Cardiology and Cardiovascular Medicine |
| topic |
mesenchymal cells MSC myocardial infarction reperfusion umbilical-cord Cardiology and Cardiovascular Medicine |
| description |
Funding Information: This work was funded by: i) national funds through FCT - Portuguese Foundation for Science and Technology, under the scope of the Cardiovascular R&D Center - UnIC (UIDB/00051/2020 and UIDP/00051/2020); ii) “la Caixa” Banking Foundation and FCT under the project code LCF/PR/HP17/52190002”; iii) the QREN project 2013/30196; and iv) the European Structural and Investment Funds (ESIF), under the Lisbon Portugal Regional Operational Program and National Funds through FCT [POCI-01-0145-FEDER-030985]. RNG and TLL were funded by the FCT individual fellowships [SFRH/BD/144490/2019] and [PD/BD/127997/2016], respectively. Funding sources had no interference in the design of the study, study governance, data collection and analysis, nor in manuscript writing or its scientific and intellectual content. Publisher Copyright: 2023 Raposo, Cerqueira, Leite, Moreira-Costa, Laundos, Miranda, Mendes-Ferreira, Coelho, Gomes, Pinto-do-Ó, Nascimento, Lourenço, Cardim and Leite-Moreira. |
| publishDate |
2023 |
| dc.date.none.fl_str_mv |
2023-06-28T22:18:24Z 2023-06 2023-06-01T00:00:00Z |
| dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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article |
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publishedVersion |
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http://hdl.handle.net/10362/154562 |
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http://hdl.handle.net/10362/154562 |
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eng |
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eng |
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2297-055X PURE: 64789697 https://doi.org/10.3389/fcvm.2023.1186574 |
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openAccess |
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