title: Combined MSC and GLP-1 Therapy Modulates Collagen Remodeling and Apoptosis following Myocardial Infarction.
abstract: Background.Mesenchymal stem cells (MSCs) and glucagon-like peptide-1 (GLP-1) are being tested as treatment strategies for myocardial infarction (MI); however, their mechanisms in the heart are not fully understood.Methods.We examined the effects of MSCs, either native, or engineered to secrete a GLP-1 fusion protein (MSCs ± GLP-1), on human cardiomyocyte apoptosisin vitro. The effect on cardiac remodeling when encapsulated in alginate beads (CellBeads-MSC and CellBeads-MSC + GLP-1) was also evaluated in a pig MI model, whereby pigs were treated with Empty Beads, CellBeads-MSC, or CellBeads-MSC + GLP-1 and sacrificed at one or four weeks following MI.Results.MSC + GLP-1 conditioned media demonstrated antiapoptotic effects on ischaemic human cardiomyocytesin vitro.In vivo,qRT-PCR revealed large changes in the expression of several genes involved in extracellular matrix remodeling, which were altered following MSC ± GLP treatment. After four weeks, infarcted areas were imaged using atomic force microscopy, demonstrating significant alterations between groups in the structure of collagen fibrils and resulting scar.Conclusions.These data demonstrate that MSCs ± GLP-1 exhibit modulatory effects on healing post-MI, affecting both apoptosis and collagen scar formation. These data support the premise that both MSCs and GLP-1 could be beneficial in MI treatment.
authors.affiliation: Division of Cardiovascular Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester M13 9NT, UK.
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Wright
authors.affiliation: Division of Cell Matrix Biology and Regenerative Medicine, Faculty of Biology, Medicine and Health, University of Manchester, Manchester M13 9NT, UK.
authors.forename: Nigel W
authors.initials: NW
authors.lastname: Hodson
authors.affiliation: Division of Cell Matrix Biology and Regenerative Medicine, Faculty of Biology, Medicine and Health, University of Manchester, Manchester M13 9NT, UK.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Sherratt
authors.affiliation: KMEB, Department of Endocrinology and Metabolism, University of Southern Denmark, 5000 Odense, Denmark.
authors.forename: Moustapha
authors.identifier: 0000-0003-1557-0869
authors.initials: M
authors.lastname: Kassem
authors.affiliation: Biocompatibles UK Ltd, Chapman House, Farnham GU9 8QL, UK.
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Lewis
authors.affiliation: CellMed AG, Industriestrasse 19, Alzenau, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Wallrapp
authors.affiliation: Division of Cardiovascular Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester M13 9NT, UK.
authors.forename: Nadim
authors.initials: N
authors.lastname: Malik
authors.affiliation: Division of Cardiovascular Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester M13 9NT, UK.
authors.forename: Cathy M
authors.identifier: 0000-0002-1517-7752
authors.initials: CM
authors.lastname: Holt