Cell and Organ Transplantology. 2022; 10(2):in press.
DOI: 10.22494/cot.v10i2.140
Stem cell therapy of myocarditis and cardiomyopathies: a promising strategy
Kovalenko V., Nesukay E.
, Cherniuk S.
, Kozliuk A.
- M. D. Strazhesko National Scientific Center of Cardiology, Clinical and Regenerative Medicine, National Academy of Medical Sciences of Ukraine, Kyiv, Ukraine
Abstract
The literature review is devoted to the analysis of modern data on the effectiveness of stem cell transplantation in patients with non-coronary heart diseases: myocarditis, dilated cardiomyopathy, and systemic amyloidosis with heart damage. The results of experimental studies on laboratory animals and clinical trials concerning the use of various types of stem cells, their mechanisms of action and prospects for application in non-coronary heart diseases are presented. Emphasis is placed on the need for further randomized multicenter clinical trials, especially in patients with inflammatory myocardial injury, involving a large number of patients.
Key words: stem cells; cell transplantation; dilated cardiomyopathy; myocarditis; amyloidosis
1. Gabrielyan AV. Comparative estimation of the efficacy for the umbilical blood stem cells transplantation and partial resection of left ventriculus in patients, suffering dilatational cardiomyopathy. Clinical surgery. 2018; 85(5): 25-29. https://doi.org/10.26779/2522-1396.2018.05.25 [In Ukrainian]. https://doi.org/10.26779/2522-1396.2018.05.25 |
||||
2. Ai JW, Liu Y, Liu CF, Pei B. Safety and efficacy of autologous bone marrow mesenchymal stem cells for dilated cardiomyopathy: a Meta-analysis. Zhongguo Zuzhi Gongcheng Yanjiu. 2017; 21(5):780-788. https://doi.org/10.3969/j.issn.2095-4344.2017.05.021 | ||||
3. Bolli R, Perin EC, Willerson JT, et al. Allogeneic Mesenchymal Cell Therapy in Anthracycline-Induced Cardiomyopathy Heart Failure Patients The CCTRN SENECA Trial. JACC:cardiooncology. 2020; 2(4):581-595. https://doi.org/10.1016/j.jaccao.2020.09.001 https://doi.org/10.1016/j.jaccao.2020.09.001 PMid:33403362 PMCid:PMC7781291 |
||||
4. Browning S, Quillen K, Sloan JM, et al. Hematologic relapse in AL amyloidosis after high-dose melphalan and stem cell transplantation. Blood. 2017; 130(11):1383-1386. https://doi.org/10.1182/blood-2017-06-788729 https://doi.org/10.1182/blood-2017-06-788729 PMid:28698204 |
||||
5. Butler J, Epstein SE, Greene SJ, et al. Intravenous Allogeneic Mesenchymal Stem Cells for Nonischemic Cardiomyopathy Safety and Efficacy Results of a Phase II-A Randomized Trial. Circulation Research. 2017; 120:332-340. https://doi.org/10.1161/CIRCRESAHA.116.309717 https://doi.org/10.1161/CIRCRESAHA.116.309717 PMid:27856497 |
||||
6. Cibeira MT, Sanchorawala V, Seldin DC, et al. Outcome of AL amyloidosis after high-dose melphalan and autologous stem cell transplantation: long-term results in a series of 421patients. Blood. 2011; 118:4346-4352. https://doi.org/10.1182/blood-2011-01-330738 https://doi.org/10.1182/blood-2011-01-330738 PMid:21828140 PMCid:PMC3204906 |
||||
7. D’Souza A, et al. Improved outcomes after autologous hematopoietic cell transplantation for light chain amyloidosis: a Center for International Blood and Marrow Transplant Research Study. J Clin Oncol. 2015; 33:3741-3749. https://doi.org/10.1200/JCO.2015.62.4015 https://doi.org/10.1200/JCO.2015.62.4015 PMid:26371138 PMCid:PMC4737858 |
||||
8. DeFilipp Z, Duarte RF, Snowden JA, et al. Metabolic syndrome and cardiovascular disease following hematopoietic cell transplantation: screening and preventive practice recommendations from CIBMTR and EBMT. Bone Marrow Transplant. 2017; 52(2):173-182. https://doi.org/10.1038/bmt.2016.203 https://doi.org/10.1038/bmt.2016.203 PMid:27548466 PMCid:PMC5288134 |
||||
9. Fitzgerald BT, Bashford J, Scalia GM. The return of the normal heart: resolution of cardiac amyloidosis after chemotherapy and bone marrow transplantation, Heart Lung Circ. 2013; 22:655-660. https://doi.org/10.1016/j.hlc.2013.01.013 https://doi.org/10.1016/j.hlc.2013.01.013 PMid:23474152 |
||||
10. Grogan M, Gertz M, McCurdy A, et al. Long term outcomes of cardiac transplant for immunoglobulin light chain amyloidosis: The Mayo Clinic experience. World J Transplant. 2016; 6(2):380-388. https://doi.org/10.5500/wjt.v6.i2.380 https://doi.org/10.5500/wjt.v6.i2.380 PMid:27358783 PMCid:PMC4919742 |
||||
11. Gu X, Li Y, Chen K, et al. Exosomes derived from umbilical cord mesenchymal stem cells alleviate viral myocarditis through activating AMPK/mTOR-mediated autophagy flux pathway. J Cell Mol Med. 2020; 24:7515-7530. https://doi.org/10.1111/jcmm.15378 https://doi.org/10.1111/jcmm.15378 PMid:32424968 PMCid:PMC7339183 |
||||
12. Guo Y, Yu Y, Hu S, et al. The therapeutic potential of mesenchymal stem cells for cardiovascular diseases. Cell Death and Disease. 2020; 11:349 https://doi.org/10.1038/s41419-020-2542-9 https://doi.org/10.1038/s41419-020-2542-9 PMid:32393744 PMCid:PMC7214402 |
||||
13. Hare JM, DiFede DL, Rieger AC, et al. Randomized Comparison of Allogeneic Versus Autologous Mesenchymal Stem Cells for Nonischemic Dilated Cardiomyopathy POSEIDON-DCM Trial. JACC. 2017; 69(5):526-537. https://doi.org/10.1016/j.jacc.2016.11.009 https://doi.org/10.1016/j.jacc.2016.11.009 PMid:27856208 PMCid:PMC5291766 |
||||
14. Hoeeg C, Frljak S, Qayyum AA, et al. Efficacy and Mode of Action of Mesenchymal Stem Cells in Non-Ischemic Dilated Cardiomyopathy: A Systematic Review Biomedicines 2020; 8:570. https://doi.org/10.3390/biomedicines8120570 https://doi.org/10.3390/biomedicines8120570 PMid:33291410 PMCid:PMC7762005 |
||||
15. Houtgraaf JH, den Dekker WK, van Dalen BM, et al. First Experience in Humans Using Adipose Tissue-Derived Regenerative Cells in the Treatment of Patients With ST-Segment Elevation Myocardial Infarction. JACC. 2012; 59 (5):539-543. https://doi.org/10.1016/j.jacc.2011.09.065 https://doi.org/10.1016/j.jacc.2011.09.065 PMid:22281257 |
||||
16. Imperlini E, Gnecchi M, Rognoni P, et al. Proteotoxicity in cardiac amyloidosis: amyloidogenic light chains affect the levels of intracellular proteins in human heart cells. Scientific Reports. 2017; 7(1):15661. https://doi.org/10.1038/s41598-017-15424-3 https://doi.org/10.1038/s41598-017-15424-3 PMid:29142197 PMCid:PMC5688098 |
||||
17. Janssens SP. Mesenchymal Cell Therapy for Dilated Cardiomyopathy. Time to Test the Water. JACC. 2017; 69(5):538-540. https://doi.org/10.1016/j.jacc.2016.11.044 https://doi.org/10.1016/j.jacc.2016.11.044 PMid:28153109 |
||||
18. Jie B, Zhang X, Wu X, Xin Y, Liu Y, Guo Y. Neuregulin-1 suppresses cardiomyocyte apoptosis by activating PI3K/Akt and inhibiting mitochondrial permeability transition pore. Molecular and cellular biochemistry. 2012; 370:35-43. https://doi.org/10.1007/s11010-012-1395-7 https://doi.org/10.1007/s11010-012-1395-7 PMid:22886427 |
||||
19. Jordan TL, Maar K, Redhage KR, et al. Light Chain Amyloidosis induced inflammatory changes in Cardiomyocytes and Adipose Derived Mesenchymal Stromal Cells. Leukemia. 2020; 34(5):1383-1393. https://doi.org/10.1038/s41375-019-0640-4 https://doi.org/10.1038/s41375-019-0640-4 PMid:31796914 PMCid:PMC7196017 |
||||
20. Karantalis V, Hare JM. Use of Mesenchymal Stem Cells for Therapy of Cardiac Disease. Circ Res. 2015; 116:1413-1430. https://doi.org/10.1161/CIRCRESAHA.116.303614 https://doi.org/10.1161/CIRCRESAHA.116.303614 PMid:25858066 PMCid:PMC4429294 |
||||
21. Kastritis E, Anagnostopoulos A, Roussou M, et al. Treatment of light chain (AL) amyloidosis with the combination of bortezomib and dexamethasone. Haematologica. 2007; 92(10):1351-1358. https://doi.org/10.3324/haematol.11325 https://doi.org/10.3324/haematol.11325 PMid:18024372 |
||||
22. Kim JY, Kim DH, Kim JH, et al. Soluble intracellular adhesion molecule-1 secreted by human umbilical cord blood-derived mesenchymal stem cell reduces amyloid-beta plaques. Cell death and differentiation. 2012 https://doi.org/10.1038/cdd.2011.140 PMid:22015609 PMCid:PMC3307982 |
||||
19(4): 680-691. https://doi.org/10.1038/cdd. 2011.140 | ||||
23. Leger KJ, Cushing-Haugen K, Hansen JA, et al. Clinical and Genetic Determinants of Cardiomyopathy Risk among Hematopoietic Cell Transplantation Survivors. Biol Blood Marrow Transplant. 2016; 22:1094-1101. https://doi.org/10.1016/j.bbmt.2016.02.017 https://doi.org/10.1016/j.bbmt.2016.02.017 PMid:26968791 PMCid:PMC4977273 |
||||
24. Li Q, Jin Y, Ye X, et al. Bone Marrow Mesenchymal Stem Cell-Derived Exosomal MicroRNA-133a Restrains Myocardial Fibrosis and Epithelial- Mesenchymal Transition in Viral Myocarditis Rats Through Suppressing MAML1. Nanoscale Res Lett. 2021; 16:111. https://doi.org/10.1186/s11671-021-03559-2 https://doi.org/10.1186/s11671-021-03559-2 PMid:34215939 PMCid:PMC8253878 |
||||
25. Lin Y, Marin-Argany M, Dick CJ et al. Mesenchymal stromal cells protect human cardiomyocytes from amyloid fibril damage. Cytotherapy. 2017; 19(12):1426-37. https://doi.org/10.1016/j.jcyt.2017.08.021 https://doi.org/10.1016/j.jcyt.2017.08.021 PMid:29037943 PMCid:PMC6456258 |
||||
26. Miteva K, Pappritz K, El-Shafeey M, et al. Mesenchymal Stromal Cells Modulate Monocytes Trafficking in Coxsackievirus B3-Induced Myocarditis. Stem Cells Translational Medicine. 2017; 6:1249-1261. https://doi.org/10.1002/sctm.16-0353 https://doi.org/10.1002/sctm.16-0353 PMid:28186704 PMCid:PMC5442851 |
||||
27. Mori D, Miyagawa S, Kido T, et al. Adipose-derived mesenchymal stem cells preserve cardiac function via ANT-1 in dilated cardiomyopathy hamster model. Regenerative Therapy. 2021; 18:182-190. https://doi.org/10.1016/j.reth.2021.06.006 https://doi.org/10.1016/j.reth.2021.06.006 PMid:34307796 PMCid:PMC8278151 |
||||
28. Nagaya N, Kangawa K, Itoh T, et al. Transplantation of Mesenchymal Stem Cells Improves Cardiac Function in a Rat Model of Dilated Cardiomyopathy. Circulation. 2005; 112:1128-1135. https://doi.org/10.1161/CIRCULATIONAHA.104.500447 https://doi.org/10.1161/CIRCULATIONAHA.104.500447 PMid:16103243 |
||||
29. Nair N, Gongora E. Stem cell therapy in heart failure: Where do we stand today? BBA-Molecular basis of the disease. 2020; 1866(4):165489. https://doi.org/10.1016/j.bbadis.2019.06.003 https://doi.org/10.1016/j.bbadis.2019.06.003 PMid:31199998 |
||||
30. Nana-Leventaki E, Nana M, Poulianitis N, et al. Cardiosphere-Derived Cells Attenuate Inflammation, Preserve Systolic Function, and Prevent Adverse Remodeling in Rat Hearts With Experimental Autoimmune Myocarditis. Journal of Cardiovascular Pharmacology and Therapeutics. 2019; 24(1):70-77. https://doi.org/10.1177/1074248418784287 https://doi.org/10.1177/1074248418784287 PMid:30060693 |
||||
31. Palladini G, Milani P. Advances in the treatment of light chain amyloidosis. Current Opinion in Oncology. 2022; 34(6):748-756. https://doi.org/10.1097/CCO.0000000000000881 https://doi.org/10.1097/CCO.0000000000000881 PMid:35943427 |
||||
32. Premer C, Wanschel A, Porras V, et al. Mesenchymal Stem Cell Secretion of SDF-1α Modulates Endothelial Function in Dilated Cardiomyopathy. Front. Physiol. 2019; 10:1182. https://doi.org/10.3389/fphys.2019.01182 https://doi.org/10.3389/fphys.2019.01182 PMid:31616309 PMCid:PMC6769040 |
||||
33. Qayyum AA, Mathiasen AB, Helqvist S, et al. Autologous adipose-derived stromal cell treatment for patients with refractory angina (MyStromalCell Trial): 3-years follow-up results. . Transl Med. 2019; 17:360. https://doi.org/10.1186/s12967-019-2110-1 https://doi.org/10.1186/s12967-019-2110-1 PMid:31711513 PMCid:PMC6849216 |
||||
34. Rieger AC, Myerburg RJ, Florea V, et al. Genetic determinants of responsiveness to mesenchymal stem cell injections in non-ischemic dilated cardiomyopathy. EBioMedicine. 2019; 48:377-385. https://doi.org/10.1016/j.ebiom.2019.09.043 https://doi.org/10.1016/j.ebiom.2019.09.043 PMid:31648988 PMCid:PMC6838383 |
||||
35. Sanchorawala V, Sun F, Quillen K, et al. Long-term outcome of patients with AL amyloidosis treated with high-dose melphalan and stem cell transplantation: 20-year experience. Blood. 2015; 126:2345-2347. https://doi.org/10.1182/blood-2015-08-662726 https://doi.org/10.1182/blood-2015-08-662726 PMid:26443620 |
||||
36. Seth S, Bhargava B, Narang R, et al. The ABCD (autologous bone marrow cells in dilated cardiomyopathy) trial, a long-term follow-up study. J Am Coll Cardiol. 2010; 55:1643-1644. https://doi.org/10.1016/j.jacc.2009.11.070 https://doi.org/10.1016/j.jacc.2009.11.070 PMid:20378086 |
||||
37. Shao M, Wang D, Zhou Y, Du K, Liu W. Interleukin-10 delivered by mesenchymal stem cells attenuates experimental autoimmune myocarditis. International Immunopharmacology. 2020; 81:106212. https://doi.org/10.1016/j.intimp.2020.106212 https://doi.org/10.1016/j.intimp.2020.106212 PMid:32062070 |
||||
38. Sidana S, Sidiqi MH, Dispenzieri A, et al. Fifteen year overall survival rates after autologous stem cell transplantation for AL amyloidosis. Am J Hematol. 2019; 94(9):1020-1026. https://doi.org/10.1002/ajh.25566.48 https://doi.org/10.1002/ajh.25566 PMid:31254301 |
||||
39. Tompkins BA, Rieger AC, Florea V, et al. Comparison of Mesenchymal Stem Cell Efficacy in Ischemic Versus Nonischemic Dilated Cardiomyopathy. J Am Heart Assoc. 2018; 7:e008460. https://doi.org/10.1161/JAHA.117.008460 https://doi.org/10.1161/JAHA.117.008460 PMid:30005555 PMCid:PMC6064862 |
||||
40. Tschope C, Miteva K, Schultheiss HP, Van Linthout S. Mesenchymal Stromal Cells: A Promising Cell Source for the Treatment of Inflammatory Cardiomyopathy. Current Pharmaceutical Design. 2011; 17: 3295-3307. https://doi.org/10.2174/138161211797904136 https://doi.org/10.2174/138161211797904136 PMid:21919878 |
||||
41. Van Linthout SV, Savvatis K, Miteva K. Mesenchymal stem cells improve murine acute coxsackievirus B3-induced myocarditis. European Heart Journal. 2011; 32:2168-2178. https://doi.org/10.1093/eurheartj/ehq467 https://doi.org/10.1093/eurheartj/ehq467 PMid:21183501 PMCid:PMC3164101 |
||||
42. Wang Y, Qi Z, Yan Z et al. Mesenchymal Stem Cell Immunomodulation: A Novel Intervention Mechanism in Cardiovascular Disease. Front Cell Dev Biol. 2022; 9:742088. https://doi.org/10.3389/fcell.2021.742088 https://doi.org/10.3389/fcell.2021.742088 PMid:35096808 PMCid:PMC8790228 |
||||
43. Wechalekar AD, Schonland SO, Kastritis E, et al. European collaborative study of treatment outcomes in 346 patients with cardiac stage III AL amyloidosis. Multicenter Study Blood. 2013; 121(17):3420-3427. https://doi.org/10.1182/blood-2012-12-473066 https://doi.org/10.1182/blood-2012-12-473066 PMid:23479568 |
||||
44. Wolfien M, Klatt D, Salybekov AA, et al. Hematopoietic stem-cell senescence and myocardial repair – Coronary artery disease genotype/phenotype analysis of post-MI myocardial regeneration response induced by CABG/CD133+ bone marrow hematopoietic stem cell treatment in RCT PERFECT Phase 3. EBioMedicine. 2020; 57:102862. https://doi.org/10.1016/j.ebiom.2020.102862 https://doi.org/10.1016/j.ebiom.2020.102862 PMid:32629392 PMCid:PMC7339012 |
||||
45. Xiao W, Guo S, Gao C, et al. A Randomized Comparative Study on the Efficacy of Intracoronary Infusion of Autologous Bone Marrow Mononuclear Cells and Mesenchymal Stem Cells in Patients With Dilated Cardiomyopathy. Int. Heart J. 2017; 58: 238-244. https://doi.org/10.1536/ihj.16-328 https://doi.org/10.1536/ihj.16-328 PMid:28190794 |
||||
46. Xu R, Zhang F, Chai R, et al. Exosomes Derived from Pro-inflammatory Bone Marrow-derived Mesenchymal Stem Cells Reduce Inflammation and Myocardial Injury via Mediating Macrophage Polarization. J. Cel Mol Med. 2019; 23: 7617-7631. https://doi.org/10.1111/jcmm.14635 https://doi.org/10.1111/jcmm.14635 PMid:31557396 PMCid:PMC6815833 |
||||
47. Yokoyama J, Miyagawa S, Akagi T, Akashi M, Sawa Y. Human induced pluripotent stem cell-derived three-dimensional cardiomyocyte tissues ameliorate the rat ischemic myocardium by remodeling the extracellular matrix and cardiac protein phenotype. PLoS ONE. 2021; 16(3):e0245571. https://doi.org/10.1371/journal. pone.0245571 https://doi.org/10.1371/journal.pone.0245571 PMid:33720933 PMCid:PMC7959395 |
||||
48. Zhang C, Zhou G, Cai C, et al. Human umbilical cord mesenchymal stem cells alleviate acute myocarditis by modulating endoplasmic reticulum stress and extracellular signal regulated 1/2-mediated apoptosis. Molecular medicine reports. 2017; 15:3515-3520. https://doi.org/10.3892/mmr.2017.6454 https://doi.org/10.3892/mmr.2017.6454 PMid:28440472 PMCid:PMC5436290 |
||||
49. Zhang C, Zhou G, Chen Y, et al. Human umbilical cord mesenchymal stem cells alleviate interstitial fibrosis and cardiac dysfunction in a dilated cardiomyopathy rat model by inhibiting TNF α and TGF β1/ERK1/2 signaling pathways Molecular medicine reports. 2018; 17:71-78. https://doi.org/10.3892/mmr.2017.7882 https://doi.org/10.3892/mmr.2017.7882 |
Kovalenko V, Nesukay E, Cherniuk S, Kozliuk A. Stem cell therapy of myocarditis and cardiomyopathies: a promising strategy. Cell Organ Transpl. 2022; 10(2):in press. doi:10.22494/cot.v10i2.140
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