Co-transplantation of Mesenchymal Stromal Cells and Induced Pluripotent Stem Cell-Derived Cardiomyocytes Improves Cardiac Function After Myocardial Damage
Induced pluripotent stem cell-derived cardiomyocytes (iPS-CMs) represent an attractive resource for cardiac regeneration. However, survival and functional integration of transplanted iPS-CM is poor and remains a major challenge for the development of effective therapies. We hypothesized that paracri...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2022-01-01
|
| Series: | Frontiers in Cardiovascular Medicine |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fcvm.2021.794690/full |
| _version_ | 1798035476106444800 |
|---|---|
| author | Klaus Neef Florian Drey Vera Lepperhof Thorsten Wahlers Jürgen Hescheler Yeong-Hoon Choi Yeong-Hoon Choi Tomo Šarić |
| author_facet | Klaus Neef Florian Drey Vera Lepperhof Thorsten Wahlers Jürgen Hescheler Yeong-Hoon Choi Yeong-Hoon Choi Tomo Šarić |
| author_sort | Klaus Neef |
| collection | DOAJ |
| description | Induced pluripotent stem cell-derived cardiomyocytes (iPS-CMs) represent an attractive resource for cardiac regeneration. However, survival and functional integration of transplanted iPS-CM is poor and remains a major challenge for the development of effective therapies. We hypothesized that paracrine effects of co-transplanted mesenchymal stromal cells (MSCs) augment the retention and therapeutic efficacy of iPS-CM in a mouse model of myocardial infarction (MI). To test this, either iPS-CM, MSC, or both cell types were transplanted into the cryoinfarction border zone of syngeneic mice immediately after injury. Bioluminescence imaging (BLI) of iPS-CM did not confirm enhanced retention by co-application of MSC during the 28-day follow-up period. However, histological analyses of hearts 28 days after cell transplantation showed that MSC increased the fraction of animals with detectable iPS-CM by 2-fold. Cardiac MRI analyses showed that from day 14 after transplantation on, the animals that have received cells had a significantly higher left ventricular ejection fraction (LVEF) compared to the placebo group. There was no statistically significant difference in LVEF between animals transplanted only with iPS-CM or only with MSC. However, combined iPS-CM and MSC transplantation resulted in higher LVEF compared to transplantation of single-cell populations during the whole observation period. Histological analyses revealed that MSC increased the capillarization in the myocardium when transplanted alone or with iPS-CM and decreased the infarct scar area only when transplanted in combination with iPS-CM. These results indicate that co-transplantation of iPS-CM and MSC improves cardiac regeneration after cardiac damage, demonstrating the potential of combining multiple cell types for increasing the efficacy of future cardiac cell therapies. |
| first_indexed | 2024-04-11T20:58:43Z |
| format | Article |
| id | doaj.art-d73242754e004034858bf8b4829931cd |
| institution | Directory Open Access Journal |
| issn | 2297-055X |
| language | English |
| last_indexed | 2024-04-11T20:58:43Z |
| publishDate | 2022-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cardiovascular Medicine |
| spelling | doaj.art-d73242754e004034858bf8b4829931cd2022-12-22T04:03:36ZengFrontiers Media S.A.Frontiers in Cardiovascular Medicine2297-055X2022-01-01810.3389/fcvm.2021.794690794690Co-transplantation of Mesenchymal Stromal Cells and Induced Pluripotent Stem Cell-Derived Cardiomyocytes Improves Cardiac Function After Myocardial DamageKlaus Neef0Florian Drey1Vera Lepperhof2Thorsten Wahlers3Jürgen Hescheler4Yeong-Hoon Choi5Yeong-Hoon Choi6Tomo Šarić7Department of Cardiac and Thoracic Surgery, Heart Center, University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, GermanyDepartment of Cardiac and Thoracic Surgery, Heart Center, University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, GermanyInstitute for Neurophysiology, Center for Physiology and Pathophysiology, University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, GermanyDepartment of Cardiac and Thoracic Surgery, Heart Center, University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, GermanyInstitute for Neurophysiology, Center for Physiology and Pathophysiology, University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, GermanyDepartment of Cardiac and Thoracic Surgery, Heart Center, University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, GermanyClinic for Cardiac Surgery and Surgical Intensive Care Medicine, Kerckhoff Clinic Bad Nauheim, Kerckhoff Campus, Justus Liebig University Giessen, Giessen, GermanyInstitute for Neurophysiology, Center for Physiology and Pathophysiology, University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, GermanyInduced pluripotent stem cell-derived cardiomyocytes (iPS-CMs) represent an attractive resource for cardiac regeneration. However, survival and functional integration of transplanted iPS-CM is poor and remains a major challenge for the development of effective therapies. We hypothesized that paracrine effects of co-transplanted mesenchymal stromal cells (MSCs) augment the retention and therapeutic efficacy of iPS-CM in a mouse model of myocardial infarction (MI). To test this, either iPS-CM, MSC, or both cell types were transplanted into the cryoinfarction border zone of syngeneic mice immediately after injury. Bioluminescence imaging (BLI) of iPS-CM did not confirm enhanced retention by co-application of MSC during the 28-day follow-up period. However, histological analyses of hearts 28 days after cell transplantation showed that MSC increased the fraction of animals with detectable iPS-CM by 2-fold. Cardiac MRI analyses showed that from day 14 after transplantation on, the animals that have received cells had a significantly higher left ventricular ejection fraction (LVEF) compared to the placebo group. There was no statistically significant difference in LVEF between animals transplanted only with iPS-CM or only with MSC. However, combined iPS-CM and MSC transplantation resulted in higher LVEF compared to transplantation of single-cell populations during the whole observation period. Histological analyses revealed that MSC increased the capillarization in the myocardium when transplanted alone or with iPS-CM and decreased the infarct scar area only when transplanted in combination with iPS-CM. These results indicate that co-transplantation of iPS-CM and MSC improves cardiac regeneration after cardiac damage, demonstrating the potential of combining multiple cell types for increasing the efficacy of future cardiac cell therapies.https://www.frontiersin.org/articles/10.3389/fcvm.2021.794690/fullmyocardial infarctioninduced pluripotent stem cellscardiomyocytesmesenchymal stem cellsimaging |
| spellingShingle | Klaus Neef Florian Drey Vera Lepperhof Thorsten Wahlers Jürgen Hescheler Yeong-Hoon Choi Yeong-Hoon Choi Tomo Šarić Co-transplantation of Mesenchymal Stromal Cells and Induced Pluripotent Stem Cell-Derived Cardiomyocytes Improves Cardiac Function After Myocardial Damage Frontiers in Cardiovascular Medicine myocardial infarction induced pluripotent stem cells cardiomyocytes mesenchymal stem cells imaging |
| title | Co-transplantation of Mesenchymal Stromal Cells and Induced Pluripotent Stem Cell-Derived Cardiomyocytes Improves Cardiac Function After Myocardial Damage |
| title_full | Co-transplantation of Mesenchymal Stromal Cells and Induced Pluripotent Stem Cell-Derived Cardiomyocytes Improves Cardiac Function After Myocardial Damage |
| title_fullStr | Co-transplantation of Mesenchymal Stromal Cells and Induced Pluripotent Stem Cell-Derived Cardiomyocytes Improves Cardiac Function After Myocardial Damage |
| title_full_unstemmed | Co-transplantation of Mesenchymal Stromal Cells and Induced Pluripotent Stem Cell-Derived Cardiomyocytes Improves Cardiac Function After Myocardial Damage |
| title_short | Co-transplantation of Mesenchymal Stromal Cells and Induced Pluripotent Stem Cell-Derived Cardiomyocytes Improves Cardiac Function After Myocardial Damage |
| title_sort | co transplantation of mesenchymal stromal cells and induced pluripotent stem cell derived cardiomyocytes improves cardiac function after myocardial damage |
| topic | myocardial infarction induced pluripotent stem cells cardiomyocytes mesenchymal stem cells imaging |
| url | https://www.frontiersin.org/articles/10.3389/fcvm.2021.794690/full |
| work_keys_str_mv | AT klausneef cotransplantationofmesenchymalstromalcellsandinducedpluripotentstemcellderivedcardiomyocytesimprovescardiacfunctionaftermyocardialdamage AT floriandrey cotransplantationofmesenchymalstromalcellsandinducedpluripotentstemcellderivedcardiomyocytesimprovescardiacfunctionaftermyocardialdamage AT veralepperhof cotransplantationofmesenchymalstromalcellsandinducedpluripotentstemcellderivedcardiomyocytesimprovescardiacfunctionaftermyocardialdamage AT thorstenwahlers cotransplantationofmesenchymalstromalcellsandinducedpluripotentstemcellderivedcardiomyocytesimprovescardiacfunctionaftermyocardialdamage AT jurgenhescheler cotransplantationofmesenchymalstromalcellsandinducedpluripotentstemcellderivedcardiomyocytesimprovescardiacfunctionaftermyocardialdamage AT yeonghoonchoi cotransplantationofmesenchymalstromalcellsandinducedpluripotentstemcellderivedcardiomyocytesimprovescardiacfunctionaftermyocardialdamage AT yeonghoonchoi cotransplantationofmesenchymalstromalcellsandinducedpluripotentstemcellderivedcardiomyocytesimprovescardiacfunctionaftermyocardialdamage AT tomosaric cotransplantationofmesenchymalstromalcellsandinducedpluripotentstemcellderivedcardiomyocytesimprovescardiacfunctionaftermyocardialdamage |