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      In vivo experience with natural scaffolds for myocardial infarction: the times they are a-changin’

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      Stem Cell Research & Therapy

      BioMed Central

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          Abstract

          Treating a myocardial infarction (MI), the most frequent cause of death worldwide, remains one of the most exciting medical challenges in the 21st century. Cardiac tissue engineering, a novel emerging treatment, involves the use of therapeutic cells supported by a scaffold for regenerating the infarcted area. It is essential to select the appropriate scaffold material; the ideal one should provide a suitable cellular microenvironment, mimic the native myocardium, and allow mechanical and electrical coupling with host tissues. Among available scaffold materials, natural scaffolds are preferable for achieving these purposes because they possess myocardial extracellular matrix properties and structures. Here, we review several natural scaffolds for applications in MI management, with a focus on pre-clinical studies and clinical trials performed to date. We also evaluate scaffolds combined with different cell types and proteins for their ability to promote improved heart function, contractility and neovascularization, and attenuate adverse ventricular remodeling. Although further refinement is necessary in the coming years, promising results indicate that natural scaffolds may be a valuable translational therapeutic option with clinical impact in MI repair.

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          Most cited references 209

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          Heart disease and stroke statistics--2015 update: a report from the American Heart Association.

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            Remodelling the extracellular matrix in development and disease.

            The extracellular matrix (ECM) is a highly dynamic structure that is present in all tissues and continuously undergoes controlled remodelling. This process involves quantitative and qualitative changes in the ECM, mediated by specific enzymes that are responsible for ECM degradation, such as metalloproteinases. The ECM interacts with cells to regulate diverse functions, including proliferation, migration and differentiation. ECM remodelling is crucial for regulating the morphogenesis of the intestine and lungs, as well as of the mammary and submandibular glands. Dysregulation of ECM composition, structure, stiffness and abundance contributes to several pathological conditions, such as fibrosis and invasive cancer. A better understanding of how the ECM regulates organ structure and function and of how ECM remodelling affects disease progression will contribute to the development of new therapeutics.
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              RGD and other recognition sequences for integrins.

               E Ruoslahti (1995)
              Proteins that contain the Arg-Gly-Asp (RGD) attachment site, together with the integrins that serve as receptors for them, constitute a major recognition system for cell adhesion. The RGD sequence is the cell attachment site of a large number of adhesive extracellular matrix, blood, and cell surface proteins, and nearly half of the over 20 known integrins recognize this sequence in their adhesion protein ligands. Some other integrins bind to related sequences in their ligands. The integrin-binding activity of adhesion proteins can be reproduced by short synthetic peptides containing the RGD sequence. Such peptides promote cell adhesion when insolubilized onto a surface, and inhibit it when presented to cells in solution. Reagents that bind selectively to only one or a few of the RGD-directed integrins can be designed by cyclizing peptides with selected sequences around the RGD and by synthesizing RGD mimics. As the integrin-mediated cell attachment influences and regulates cell migration, growth, differentiation, and apoptosis, the RGD peptides and mimics can be used to probe integrin functions in various biological systems. Drug design based on the RGD structure may provide new treatments for diseases such as thrombosis, osteoporosis, and cancer.
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                Author and article information

                Contributors
                cprat@igtp.cat
                Journal
                Stem Cell Res Ther
                Stem Cell Res Ther
                Stem Cell Research & Therapy
                BioMed Central (London )
                1757-6512
                6 December 2015
                6 December 2015
                2015
                : 6
                Affiliations
                [ ]ICREC (Heart Failure and Cardiac Regeneration) Research Lab, Health Sciences Research Institute Germans Trias i Pujol (IGTP). Cardiology Service, Hospital Universitari Germans Trias i Pujol, 08916 Badalona, Barcelona Spain
                [ ]Department of Medicine, Autonomous University of Barcelona (UAB), Barcelona, Spain
                Article
                237
                10.1186/s13287-015-0237-4
                4681026
                © Perea-Gil et al. 2015

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                Funding
                Funded by: Red de Investigación Cardiovascular
                Award ID: RD12/0042/0047
                Award Recipient :
                Funded by: Red de Investigación en Terapia Celular-TerCel
                Award ID: RD12/0019-/0029
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/501100004587, Instituto de Salud Carlos III;
                Award ID: FIS-PI14/01682
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/501100004837, Ministerio de Ciencia e Innovación;
                Award ID: SAF-2011-30067-C02-01/02
                Award Recipient :
                Funded by: Fundació Privada Daniel Bravo Andreu
                Award ID: ---
                Award Recipient :
                Funded by: La Marató de TV3
                Award ID: 12/2232
                Award Recipient :
                Funded by: Medical Sciences and Health Academy of Catalonia and Balearics
                Award ID: ---
                Award Recipient :
                Funded by: Catalan Society of Cardiology
                Award ID: ---
                Award Recipient :
                Funded by: Spanish Society of Cardiology
                Award ID: ---
                Award Recipient :
                Categories
                Review
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                © The Author(s) 2015

                Molecular medicine

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