Combined MSC and GLP-1 Therapy Modulates Collagen Remodeling and Apoptosis following Myocardial Infarction
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...
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| Format: | Article |
| Language: | English |
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Wiley
2016-01-01
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| Series: | Stem Cells International |
| Online Access: | http://dx.doi.org/10.1155/2016/7357096 |
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| author | Elizabeth J. Wright Nigel W. Hodson Michael J. Sherratt Moustapha Kassem Andrew L. Lewis Christine Wallrapp Nadim Malik Cathy M. Holt |
| author_facet | Elizabeth J. Wright Nigel W. Hodson Michael J. Sherratt Moustapha Kassem Andrew L. Lewis Christine Wallrapp Nadim Malik Cathy M. Holt |
| author_sort | Elizabeth J. Wright |
| collection | DOAJ |
| description | 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 apoptosis in 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 cardiomyocytes in 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. |
| format | Article |
| id | doaj-art-5a3d799a70b649eebeb6f93fa7285d6e |
| institution | Kabale University |
| issn | 1687-966X 1687-9678 |
| language | English |
| publishDate | 2016-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Stem Cells International |
| spelling | doaj-art-5a3d799a70b649eebeb6f93fa7285d6e2025-02-03T05:50:08ZengWileyStem Cells International1687-966X1687-96782016-01-01201610.1155/2016/73570967357096Combined MSC and GLP-1 Therapy Modulates Collagen Remodeling and Apoptosis following Myocardial InfarctionElizabeth J. Wright0Nigel W. Hodson1Michael J. Sherratt2Moustapha Kassem3Andrew L. Lewis4Christine Wallrapp5Nadim Malik6Cathy M. Holt7Division of Cardiovascular Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester M13 9NT, UKDivision of Cell Matrix Biology and Regenerative Medicine, Faculty of Biology, Medicine and Health, University of Manchester, Manchester M13 9NT, UKDivision of Cell Matrix Biology and Regenerative Medicine, Faculty of Biology, Medicine and Health, University of Manchester, Manchester M13 9NT, UKKMEB, Department of Endocrinology and Metabolism, University of Southern Denmark, 5000 Odense, DenmarkBiocompatibles UK Ltd, Chapman House, Farnham GU9 8QL, UKCellMed AG, Industriestrasse 19, Alzenau, GermanyDivision of Cardiovascular Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester M13 9NT, UKDivision of Cardiovascular Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester M13 9NT, UKBackground. 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 apoptosis in 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 cardiomyocytes in 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.http://dx.doi.org/10.1155/2016/7357096 |
| spellingShingle | Elizabeth J. Wright Nigel W. Hodson Michael J. Sherratt Moustapha Kassem Andrew L. Lewis Christine Wallrapp Nadim Malik Cathy M. Holt Combined MSC and GLP-1 Therapy Modulates Collagen Remodeling and Apoptosis following Myocardial Infarction Stem Cells International |
| title | Combined MSC and GLP-1 Therapy Modulates Collagen Remodeling and Apoptosis following Myocardial Infarction |
| title_full | Combined MSC and GLP-1 Therapy Modulates Collagen Remodeling and Apoptosis following Myocardial Infarction |
| title_fullStr | Combined MSC and GLP-1 Therapy Modulates Collagen Remodeling and Apoptosis following Myocardial Infarction |
| title_full_unstemmed | Combined MSC and GLP-1 Therapy Modulates Collagen Remodeling and Apoptosis following Myocardial Infarction |
| title_short | Combined MSC and GLP-1 Therapy Modulates Collagen Remodeling and Apoptosis following Myocardial Infarction |
| title_sort | combined msc and glp 1 therapy modulates collagen remodeling and apoptosis following myocardial infarction |
| url | http://dx.doi.org/10.1155/2016/7357096 |
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