Multi-modal assessment of a cardiac stem cell therapy reveals distinct modulation of regional scar properties
Abstract Background The initial idea of functional tissue replacement has shifted to the concept that injected cells positively modulate myocardial healing by a non-specific immune response of the transplanted cells within the target tissue. This alleged local modification of the scar requires asses...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2024-02-01
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| Series: | Journal of Translational Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12967-024-04986-2 |
| _version_ | 1797273493120745472 |
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| author | Moritz Schweins Ralf Gäbel Matti Raitza Praveen Vasudevan Heiko Lemcke Markus Joksch Anna Schildt Jens Kurth Tobias Lindner Felix G. Meinel Alper Öner Hüseyin Ince Brigitte Vollmar Bernd Joachim Krause Robert David Cajetan Immanuel Lang |
| author_facet | Moritz Schweins Ralf Gäbel Matti Raitza Praveen Vasudevan Heiko Lemcke Markus Joksch Anna Schildt Jens Kurth Tobias Lindner Felix G. Meinel Alper Öner Hüseyin Ince Brigitte Vollmar Bernd Joachim Krause Robert David Cajetan Immanuel Lang |
| author_sort | Moritz Schweins |
| collection | DOAJ |
| description | Abstract Background The initial idea of functional tissue replacement has shifted to the concept that injected cells positively modulate myocardial healing by a non-specific immune response of the transplanted cells within the target tissue. This alleged local modification of the scar requires assessment of regional properties of the left ventricular wall in addition to commonly applied measures of global morphological and functional parameters. Hence, we aimed at investigating the effect of cardiac cell therapy with cardiovascular progenitor cells, so-called cardiac induced cells, on both global and regional properties of the left ventricle by a multimodal imaging approach in a mouse model. Methods Myocardial infarction was induced in mice by ligation of the left anterior descending artery, the therapy group received an intramyocardial injection of 1 × 106 cardiac induced cells suspended in matrigel, the control group received matrigel only. [18F]FDG positron emission tomography imaging was performed after 17 days, to assess regional glucose metabolism. Three weeks after myocardial infarction, cardiac magnetic resonance imaging was performed for morphological and functional assessment of the left ventricle. Following these measurements, hearts were excised for histological examinations. Results Cell therapy had no significant effect on global morphological parameters. Similarly, there was no difference in scar size and capillary density between therapy and control group. However, there was a significant improvement in contractile function of the left ventricle – left ventricular ejection fraction, stroke volume and cardiac output. Regional analysis of the left ventricle identified changes of wall properties in the scar area as the putative mechanism. Cell therapy reduced the thinning of the scar and significantly improved its radial contractility. Furthermore, the metabolic defect, assessed by [18F]FDG, was significantly reduced by the cell therapy. Conclusion Our data support the relevance of extending the assessment of global left ventricular parameters by a structured regional wall analysis for the evaluation of therapies targeting at modulation of healing myocardium. This approach will enable a deeper understanding of mechanisms underlying the effect of experimental regenerative therapies, thus paving the way for a successful translation into clinical application. |
| first_indexed | 2024-03-07T14:44:05Z |
| format | Article |
| id | doaj.art-d4f4b7deaea14d3b9933b1f46db2fc8a |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-03-07T14:44:05Z |
| publishDate | 2024-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-d4f4b7deaea14d3b9933b1f46db2fc8a2024-03-05T20:06:18ZengBMCJournal of Translational Medicine1479-58762024-02-012211910.1186/s12967-024-04986-2Multi-modal assessment of a cardiac stem cell therapy reveals distinct modulation of regional scar propertiesMoritz Schweins0Ralf Gäbel1Matti Raitza2Praveen Vasudevan3Heiko Lemcke4Markus Joksch5Anna Schildt6Jens Kurth7Tobias Lindner8Felix G. Meinel9Alper Öner10Hüseyin Ince11Brigitte Vollmar12Bernd Joachim Krause13Robert David14Cajetan Immanuel Lang15Department of Cardiac Surgery, Rostock University Medical CentreDepartment of Cardiac Surgery, Rostock University Medical CentreDepartment of Cardiac Surgery, Rostock University Medical CentreDepartment of Cardiac Surgery, Rostock University Medical CentreDepartment of Cardiac Surgery, Rostock University Medical CentreDepartment of Nuclear Medicine, Rostock University Medical CentreCore Facility Multimodal Small Animal Imaging, Rostock University Medical CentreDepartment of Nuclear Medicine, Rostock University Medical CentreCore Facility Multimodal Small Animal Imaging, Rostock University Medical CentreInstitute of Diagnostic and Interventional Radiology, Rostock University Medical CenterDepartment of Cardiology, Rostock University Medical CentreDepartment of Cardiology, Rostock University Medical CentreRudolf-Zenker-Institute for Experimental Surgery, Rostock University Medical CentreDepartment of Nuclear Medicine, Rostock University Medical CentreDepartment of Cardiac Surgery, Rostock University Medical CentreDepartment of Cardiology, Rostock University Medical CentreAbstract Background The initial idea of functional tissue replacement has shifted to the concept that injected cells positively modulate myocardial healing by a non-specific immune response of the transplanted cells within the target tissue. This alleged local modification of the scar requires assessment of regional properties of the left ventricular wall in addition to commonly applied measures of global morphological and functional parameters. Hence, we aimed at investigating the effect of cardiac cell therapy with cardiovascular progenitor cells, so-called cardiac induced cells, on both global and regional properties of the left ventricle by a multimodal imaging approach in a mouse model. Methods Myocardial infarction was induced in mice by ligation of the left anterior descending artery, the therapy group received an intramyocardial injection of 1 × 106 cardiac induced cells suspended in matrigel, the control group received matrigel only. [18F]FDG positron emission tomography imaging was performed after 17 days, to assess regional glucose metabolism. Three weeks after myocardial infarction, cardiac magnetic resonance imaging was performed for morphological and functional assessment of the left ventricle. Following these measurements, hearts were excised for histological examinations. Results Cell therapy had no significant effect on global morphological parameters. Similarly, there was no difference in scar size and capillary density between therapy and control group. However, there was a significant improvement in contractile function of the left ventricle – left ventricular ejection fraction, stroke volume and cardiac output. Regional analysis of the left ventricle identified changes of wall properties in the scar area as the putative mechanism. Cell therapy reduced the thinning of the scar and significantly improved its radial contractility. Furthermore, the metabolic defect, assessed by [18F]FDG, was significantly reduced by the cell therapy. Conclusion Our data support the relevance of extending the assessment of global left ventricular parameters by a structured regional wall analysis for the evaluation of therapies targeting at modulation of healing myocardium. This approach will enable a deeper understanding of mechanisms underlying the effect of experimental regenerative therapies, thus paving the way for a successful translation into clinical application.https://doi.org/10.1186/s12967-024-04986-2Mouse modelMyocardial infarctionCell therapyRegional wall analysis |
| spellingShingle | Moritz Schweins Ralf Gäbel Matti Raitza Praveen Vasudevan Heiko Lemcke Markus Joksch Anna Schildt Jens Kurth Tobias Lindner Felix G. Meinel Alper Öner Hüseyin Ince Brigitte Vollmar Bernd Joachim Krause Robert David Cajetan Immanuel Lang Multi-modal assessment of a cardiac stem cell therapy reveals distinct modulation of regional scar properties Journal of Translational Medicine Mouse model Myocardial infarction Cell therapy Regional wall analysis |
| title | Multi-modal assessment of a cardiac stem cell therapy reveals distinct modulation of regional scar properties |
| title_full | Multi-modal assessment of a cardiac stem cell therapy reveals distinct modulation of regional scar properties |
| title_fullStr | Multi-modal assessment of a cardiac stem cell therapy reveals distinct modulation of regional scar properties |
| title_full_unstemmed | Multi-modal assessment of a cardiac stem cell therapy reveals distinct modulation of regional scar properties |
| title_short | Multi-modal assessment of a cardiac stem cell therapy reveals distinct modulation of regional scar properties |
| title_sort | multi modal assessment of a cardiac stem cell therapy reveals distinct modulation of regional scar properties |
| topic | Mouse model Myocardial infarction Cell therapy Regional wall analysis |
| url | https://doi.org/10.1186/s12967-024-04986-2 |
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