Cardiac Cell Therapy: Insights into the Mechanisms of Tissue Repair
Abstract
:1. Introduction
2. Stem Cells as Cardiac Immunomodulatory Therapy
2.1. Immunoregulatory Function of Mesenchymal Stem/Stromal Cells (MSCs)
2.1.1. Immunoregulatory Effects of MSCs on Neutrophils
2.1.2. Immunoregulatory Effects of MSCs on Macrophage
2.1.3. Immunoregulatory Effects of MSCs on Lymphocytes
2.2. Immunomodulatory Properties of Cardiosphere-Derived Cells (CDCs)
3. MSC Therapy in Clinical Trials
3.1. Acute Myocardial Infarction (AMI)
3.2. Chronic Heart Failure Reduced Ejection Fraction (Chronic HFrEF)
4. Cardiosphere Derived Stem Cells (CDCs)
5. Future Perspectives
6. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Conflicts of Interest
References
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Study Name | Year | Disease | Study Type | Cell Type | n | Follow Up | Results |
---|---|---|---|---|---|---|---|
AMI | |||||||
Chen et al. [71] | 2004 | AMI | Randomized, PC | Autologous BMMSCs | 69 | 6 m | Improved LVEF and myocardial perfusion |
Hare et al. [72] | 2009 | AMI | Randomized, DB, PC | Allogeneic BMMSCs | 53 | 6 m | Improved LVEF and symptoms |
APOLLO [76] | 2012 | AMI | Randomized, DB, PC | Autologous ADSCs | 14 | 6 m | Improved perfusion and scar formation |
Lee et al. [73] | 2014 | AMI | Randomized, No PC | Autologous BMMSCs | 58 | 6 m | Improved LVEF |
Gao et al. [78] | 2015 | STEMI | Randomized, DB, PC | UC-MSCs | 116 | 18 m | Improved LVEF, LV volumes, perfusion |
Chronic HFrEF | |||||||
POSEIDON [73] | 2012 | ICM with LVEF < 50 | Randomized, No PC | Autologous or Allogeneic BMMSCs | 30 | 13 m | Autologous MSCs-improved 6 mw and reduced infarct size |
Allogenic MSCs-improved LVEDV and reduced infarct size | |||||||
C-CURE [82] | 2013 | ICM with LVEF < 40, | Randomized, No PC | Autologous cardiac preconditioned BMMSCs | 47 | 2 y | Improved LVEF, LVESV, and symptoms |
NYHA 2 or 3 | |||||||
TAC-HFT [75] | 2014 | ICM with LVEF < 50 | Randomized, DB, PC | Autologous BMMNCs or MSCs | 65 | 12 m | MSCs-improved symptom, 6 mw, and reduced infarct size. |
BMMNCs-improved symptom and regional myocardial function | |||||||
Ascheim et al. [76] | 2014 | Chronic HFrEF with LVAD | Randomized, DB, PC | Allogeneic BMMSCs | 30 | 12 m | No significant difference between treatments |
PRECISE [83] | 2014 | ICM with NYHA 2-3 | Randomized, DB, PC | Autologous ADSCs | 27 | 36 m | Preserved MVO2, improved LV mass and wall motion score index |
PROMETHEUS [77] | 2014 | ICM, CABG | Randomized, No PC | Autologous BMMSCs | 6 | 18 m | Reduced infarct size |
MSC-HF [78] | 2015 | ICM with NYHA 2-3, | Randomized, DB, PC | Autologous BMMSCs | 55 | 6 m | Improved LVEF and LV volumes, symptom |
LVEF < 45 | |||||||
Perin et al. [79] | 2015 | Chronic HFrEF | Randomized, DB, PC | Allogeneic BMMSCs | 60 | 3 y | Improved mortality and HF-related MACE |
MESAMI1 pilot [80] | 2016 | ICM with LVEF < 35 | No randomized | Autologous BMMSCs | 10 | 2 y | Improved LVEF and LV volumes |
CHART-1 [84] | 2017 | ICM with LVEF < 35, | Randomized, DB, PC | Autologous cardiac preconditioned BMMSCs | 271 | 39 w | No significant different |
NYHA 2-4 | (Patient with LVEDV 200-370mL-improved 6mw) | ||||||
RIMECARD [85] | 2017 | Chronic HFrEF | Randomized, DB, PC | UC-MSCs | 30 | 12 m | Improved symptoms and LVEF |
with NYHA 1-3, LVEF < 40 | |||||||
POSEIDON-DCM [74] | 2017 | NIDCM with LVEF < 40 | Randomized, No PC | Autologous or Allogeneic BMMSCs | 37 | 12 m | Improved LVEF (Autologous vs. Allogenic: no significant difference) and 6 min walk test (Autologous better than Allogenic). |
TRIDENT [81] | 2017 | ICM | Randomized, DB, PC | Allogeneic BMMSCs | 60 | 12 m | Improved infarct size, symptom |
HUC-HEART [86] | 2020 | ICM with CABG, | Randomized, SB, No PC | UC-MSCs or BMMNCs | 46 | 12 m | UC-MSCs-improved EF, SV, 6 mw, and reduced infarct size |
LVEF < 45 | BMMNCs–reduced infarct size |
Study Name | Year | Disease | Study Type | Cell Type | n | Follow Up | Results |
---|---|---|---|---|---|---|---|
CADUCEUS [51,52] | 2014 | ICM | Randomized, No PC | Autologous CDCs | 25 | 1 y | Improved scar size, viable heart mass, regional contractility, regional systolic wall thickening |
DYNAMIC [88] | 2020 | HFrEF | No Randomized | Allogeneic CDCs | 14 | 1 y | Improved LVEF, QOL |
ALLSTAR [89] | 2020 | ICM | Randomized, DB, PC, | Allogeneic CDCs | 134 | 6 m | Improved LVEDV, LVESV, decreased plasma BNP |
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Peng, H.; Shindo, K.; Donahue, R.R.; Abdel-Latif, A. Cardiac Cell Therapy: Insights into the Mechanisms of Tissue Repair. Int. J. Mol. Sci. 2021, 22, 1201. https://doi.org/10.3390/ijms22031201
Peng H, Shindo K, Donahue RR, Abdel-Latif A. Cardiac Cell Therapy: Insights into the Mechanisms of Tissue Repair. International Journal of Molecular Sciences. 2021; 22(3):1201. https://doi.org/10.3390/ijms22031201
Chicago/Turabian StylePeng, Hsuan, Kazuhiro Shindo, Renée R. Donahue, and Ahmed Abdel-Latif. 2021. "Cardiac Cell Therapy: Insights into the Mechanisms of Tissue Repair" International Journal of Molecular Sciences 22, no. 3: 1201. https://doi.org/10.3390/ijms22031201