Feasibility of Intracoronary GLP-1 Eluting CellBead Infusion in Acute Myocardial Infarction
Cell therapy is a field of growing interest in the prevention of post acute myocardial infarction (AMI) heart failure. Stem cell retention upon local delivery to the heart, however, is still unsatisfactory. CellBeads were recently developed as a potential solution to this problem. CellBeads are 170-...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
SAGE Publishing
2013-03-01
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| Series: | Cell Transplantation |
| Online Access: | https://doi.org/10.3727/096368912X638973 |
| _version_ | 1819296314215628800 |
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| author | Jaco H. Houtgraaf Renate De Jong Kim Monkhorst Dennie Tempel Esther Van De Kamp Wijnand K. Den Dekker Kushan Kazemi Imo Hoefer Gerard Pasterkamp Andrew L. Lewis Peter W. Stratford Christine Wallrapp Felix Zijlstra Henricus J. Duckers M.D., Ph.D., FESC, FACC |
| author_facet | Jaco H. Houtgraaf Renate De Jong Kim Monkhorst Dennie Tempel Esther Van De Kamp Wijnand K. Den Dekker Kushan Kazemi Imo Hoefer Gerard Pasterkamp Andrew L. Lewis Peter W. Stratford Christine Wallrapp Felix Zijlstra Henricus J. Duckers M.D., Ph.D., FESC, FACC |
| author_sort | Jaco H. Houtgraaf |
| collection | DOAJ |
| description | Cell therapy is a field of growing interest in the prevention of post acute myocardial infarction (AMI) heart failure. Stem cell retention upon local delivery to the heart, however, is still unsatisfactory. CellBeads were recently developed as a potential solution to this problem. CellBeads are 170-μm alginate microspheres that contain mesenchymal stem cells (MSCs) genetically modified to express glucagon-like peptide-1 (GLP-1) supplementary to inherent paracrine factors. GLP-1 is an incretin hormone that has both antiapoptotic and cardioprotective effects. Transplanting CellBeads in the post-AMI heart might induce cardiomyocyte salvage and ultimately abrogate adverse cardiac remodeling. We aimed to investigate the feasibility of intracoronary infusion of CellBeads in a large animal model of AMI. Four pigs were used in a pilot study to assess the maximal safe dose of CellBeads. In the remaining 21 animals, an AMI was induced by balloon occlusion of the left circumflex coronary artery for 90 min. During reperfusion, 60,000 CellBeads ( n = 11), control beads ( n = 4), or lactated Ringers' ( n = 6) were infused. Animals were sacrificed after 2 or 7 days, and the hearts were excised for histological analyses. Intracoronary infusion did not permanently affect coronary flow in any of the groups. Histological analysis revealed CellBeads containing viable MSCs up to 7 days. Viability and activity of the MSCs was confirmed by qPCR analysis that showed expression of recombinant GLP-1 and human genes after 2 and 7 days. CellBeads reduced inflammatory infiltration by 29% ( p = 0.001). In addition, they decreased the extent of apoptosis by 25% ( p = 0.001) after 2 days. We show that intracoronary infusion of 5 million encapsulated MSCs is safe and feasible. Also, several parameters indicate that the cells have paracrine effects, suggesting a potential therapeutic benefit of this new approach. |
| first_indexed | 2024-12-24T04:56:08Z |
| format | Article |
| id | doaj.art-33492ae1a2d446cca231c1e070c63b98 |
| institution | Directory Open Access Journal |
| issn | 0963-6897 1555-3892 |
| language | English |
| last_indexed | 2024-12-24T04:56:08Z |
| publishDate | 2013-03-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Cell Transplantation |
| spelling | doaj.art-33492ae1a2d446cca231c1e070c63b982022-12-21T17:14:23ZengSAGE PublishingCell Transplantation0963-68971555-38922013-03-012210.3727/096368912X638973Feasibility of Intracoronary GLP-1 Eluting CellBead Infusion in Acute Myocardial InfarctionJaco H. Houtgraaf0Renate De Jong1Kim Monkhorst2Dennie Tempel3Esther Van De Kamp4Wijnand K. Den Dekker5Kushan Kazemi6Imo Hoefer7Gerard Pasterkamp8Andrew L. Lewis9Peter W. Stratford10Christine Wallrapp11Felix Zijlstra12Henricus J. Duckers M.D., Ph.D., FESC, FACC13Molecular Cardiology Laboratory, Thoraxcenter, Erasmus University Medical Center Rotterdam, Rotterdam, The NetherlandsMolecular Cardiology Laboratory, Thoraxcenter, Erasmus University Medical Center Rotterdam, Rotterdam, The NetherlandsDepartment of Pathology, Erasmus University Medical Center Rotterdam, Rotterdam, The NetherlandsMolecular Cardiology Laboratory, Thoraxcenter, Erasmus University Medical Center Rotterdam, Rotterdam, The NetherlandsMolecular Cardiology Laboratory, Thoraxcenter, Erasmus University Medical Center Rotterdam, Rotterdam, The NetherlandsMolecular Cardiology Laboratory, Thoraxcenter, Erasmus University Medical Center Rotterdam, Rotterdam, The NetherlandsMolecular Cardiology Laboratory, Thoraxcenter, Erasmus University Medical Center Rotterdam, Rotterdam, The NetherlandsExperimental Cardiology, University Hospital Utrecht, Utrecht, The NetherlandsExperimental Cardiology, University Hospital Utrecht, Utrecht, The NetherlandsBiocompatibles UK Ltd., Farnham, UKBiocompatibles UK Ltd., Farnham, UKCellMed AG, Alzenau, GermanyDepartment of Cardiology, Thoraxcenter, Erasmus University Medical Center Rotterdam, Rotterdam, The NetherlandsMolecular Cardiology Laboratory, Thoraxcenter, Erasmus University Medical Center Rotterdam, Rotterdam, The NetherlandsCell therapy is a field of growing interest in the prevention of post acute myocardial infarction (AMI) heart failure. Stem cell retention upon local delivery to the heart, however, is still unsatisfactory. CellBeads were recently developed as a potential solution to this problem. CellBeads are 170-μm alginate microspheres that contain mesenchymal stem cells (MSCs) genetically modified to express glucagon-like peptide-1 (GLP-1) supplementary to inherent paracrine factors. GLP-1 is an incretin hormone that has both antiapoptotic and cardioprotective effects. Transplanting CellBeads in the post-AMI heart might induce cardiomyocyte salvage and ultimately abrogate adverse cardiac remodeling. We aimed to investigate the feasibility of intracoronary infusion of CellBeads in a large animal model of AMI. Four pigs were used in a pilot study to assess the maximal safe dose of CellBeads. In the remaining 21 animals, an AMI was induced by balloon occlusion of the left circumflex coronary artery for 90 min. During reperfusion, 60,000 CellBeads ( n = 11), control beads ( n = 4), or lactated Ringers' ( n = 6) were infused. Animals were sacrificed after 2 or 7 days, and the hearts were excised for histological analyses. Intracoronary infusion did not permanently affect coronary flow in any of the groups. Histological analysis revealed CellBeads containing viable MSCs up to 7 days. Viability and activity of the MSCs was confirmed by qPCR analysis that showed expression of recombinant GLP-1 and human genes after 2 and 7 days. CellBeads reduced inflammatory infiltration by 29% ( p = 0.001). In addition, they decreased the extent of apoptosis by 25% ( p = 0.001) after 2 days. We show that intracoronary infusion of 5 million encapsulated MSCs is safe and feasible. Also, several parameters indicate that the cells have paracrine effects, suggesting a potential therapeutic benefit of this new approach.https://doi.org/10.3727/096368912X638973 |
| spellingShingle | Jaco H. Houtgraaf Renate De Jong Kim Monkhorst Dennie Tempel Esther Van De Kamp Wijnand K. Den Dekker Kushan Kazemi Imo Hoefer Gerard Pasterkamp Andrew L. Lewis Peter W. Stratford Christine Wallrapp Felix Zijlstra Henricus J. Duckers M.D., Ph.D., FESC, FACC Feasibility of Intracoronary GLP-1 Eluting CellBead Infusion in Acute Myocardial Infarction Cell Transplantation |
| title | Feasibility of Intracoronary GLP-1 Eluting CellBead Infusion in Acute Myocardial Infarction |
| title_full | Feasibility of Intracoronary GLP-1 Eluting CellBead Infusion in Acute Myocardial Infarction |
| title_fullStr | Feasibility of Intracoronary GLP-1 Eluting CellBead Infusion in Acute Myocardial Infarction |
| title_full_unstemmed | Feasibility of Intracoronary GLP-1 Eluting CellBead Infusion in Acute Myocardial Infarction |
| title_short | Feasibility of Intracoronary GLP-1 Eluting CellBead Infusion in Acute Myocardial Infarction |
| title_sort | feasibility of intracoronary glp 1 eluting cellbead infusion in acute myocardial infarction |
| url | https://doi.org/10.3727/096368912X638973 |
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