Stem cell therapy in treatment of heart failure – a literature review
DOI:
https://doi.org/10.12775/QS.2025.39.58908Keywords
ischaemic heart failure, myocardial infarction, stem cell therapy, heart failure, adipose stem cellAbstract
Introduction
Heart failure is a condition defined as insufficient supply of oxygen to tissues, caused by a reduced cardiac output. It is usually associated with myocardial infarction or valve malfunction, but can also be a result of chronic diseases, such as hypertension or alcohol abuse. Despite the good state of knowledge about this disease and modern forms of treatment, heart failure remains a major therapeutic problem and a common cause of death around the world. The evolution of heart failure treatment over the years has revolved around managing the symptoms, yet failed to develop a causal treatment. Stem cell therapy has risen interest among researchers, as promising studies had emerged. The regenerative potential of stem cells and their paracrine properties are believed to improve cardiac function in patients with heart failure.
Aim of study
The aim of this study is to review randomized clinical trials published in the last 5 years and evaluate the safety and potential role of stem cell therapy in managing patients suffering from heart failure.
State of knowledge
Stem cells are capable of self-renewal and differentiating into other types of cells. They hold great promise in the field of regenerative medicine as a factor inducing tissue repair, reducing apoptosis and promoting angiogenesis. Animal studies have shown their positive effect on cardiac contractility and also reducing the amount of scar tissue, but subsequent studies in humans have not yielded consistent results.
Conclusion
Heart failure therapy using stem cells is a safe method. Promising results of clinical studies have been reported related to the improvement of contractile function of the heart, as well as reduction of scar mass and improvement of quality of life. However, there is still a lack of consistent data and guidelines regarding the selection of the type of cells and the method of their administration. This topic requires broader studies, on larger groups of patients.
References
1. Qayyum, A.A., van Klarenbosch, B., Frljak, S., Cerar, A., Poglajen, G., Traxler-Weidenauer, D., Nadrowski, P., Paitazoglou, C., Vrtovec, B., Bergmann, M.W., Chamuleau, S.A.J., Wojakowski, W., Gyöngyösi, M., Kraaijeveld, A., Hansen, K.S., Vrangbæk, K., Jørgensen, E., Helqvist, S., Joshi, F.R., Johansen, E.M., Follin, B., Juhl, M., Højgaard, L.D., Mathiasen, A.B., Ekblond, A., Haack-Sørensen, M., Kastrup, J. and (2023), Effect of allogeneic adipose tissue-derived mesenchymal stromal cell treatment in chronic ischaemic heart failure with reduced ejection fraction – the SCIENCE trial. Eur J Heart Fail, 25: 576-587. https://doi.org/10.1002/ejhf.2772
2. Mathiasen, A.B., Qayyum, A.A., Jørgensen, E., Helqvist, S., Kofoed, K.F., Haack-Sørensen, M., Ekblond, A. and Kastrup, J. (2020), Bone marrow-derived mesenchymal stromal cell treatment in patients with ischaemic heart failure: final 4-year follow-up of the MSC-HF trial. Eur J Heart Fail, 22: 884-892. https://doi.org/10.1002/ejhf.1700
3. Bolli, R., Mitrani, R.D., Hare, J.M., Pepine, C.J., Perin, E.C., Willerson, J.T., Traverse, J.H., Henry, T.D., Yang, P.C., Murphy, M.P., March, K.L., Schulman, I.H., Ikram, S., Lee, D.P., O'Brien, C., Lima, J.A., Ostovaneh, M.R., Ambale-Venkatesh, B., Lewis, G., Khan, A., Bacallao, K., Valasaki, K., Longsomboon, B., Gee, A.P., Richman, S., Taylor, D.A., Lai, D., Sayre, S.L., Bettencourt, J., Vojvodic, R.W., Cohen, M.L., Simpson, L., Aguilar, D., Loghin, C., Moyé, L., Ebert, R.F., Davis, B.R., Simari, R.D. and (2021), A Phase II study of autologous mesenchymal stromal cells and c-kit positive cardiac cells, alone or in combination, in patients with ischaemic heart failure: the CCTRN CONCERT-HF trial. Eur J Heart Fail, 23: 661-674. https://doi.org/10.1002/ejhf.2178
4. Soetisna, T. W. (2021). CD133+ Stem Cell Therapy Effects on Myocardial Regeneration Through Increased Vascular Endothelial Growth Factor Correlate with Cardiac Magnetic Resonance Imaging Results in Coronary Artery Bypass Graft Surgery Patients with Low Ejection Fraction. The Heart Surgery Forum, 24(4), E670-E674. https://doi.org/10.1532/hsf.3763
5. Kawamura, T., Yoshioka, D., Kawamura, A. et al. Safety and therapeutic potential of allogeneic adipose-derived stem cell spray transplantation in ischemic cardiomyopathy: a phase I clinical trial. J Transl Med 22, 1091 (2024). https://doi.org/10.1186/s12967-024-05816-1
6. Qayyum, A. A., Mouridsen, M., Nilsson, B., Gustafsson, I., Schou, M., Nielsen, O. W., Hove, J. D., Mathiasen, A. B., Jørgensen, E., Helqvist, S., Joshi, F. R., Johansen, E. M., Follin, B., Juhl, M., Højgaard, L. D., Haack-Sørensen, M., Ekblond, A., and Kastrup, J. (2023) Danish phase II trial using adipose tissue derived mesenchymal stromal cells for patients with ischaemic heart failure. ESC Heart Failure, 10: 1170–1183. https://doi.org/10.1002/ehf2.14281
7. Raj R Makkar, Dean J Kereiakes, Frank Aguirre, Glenn Kowalchuk, Tarun Chakravarty, Konstantinos Malliaras, Gary S Francis, Thomas J Povsic, Richard Schatz, Jay H Traverse, Janice M Pogoda, Rachel R Smith, Linda Marbán, Deborah D Ascheim, Mohammad R Ostovaneh, João A C Lima, Anthony DeMaria, Eduardo Marbán, Timothy D Henry, Intracoronary ALLogeneic heart STem cells to Achieve myocardial Regeneration (ALLSTAR): a randomized, placebo-controlled, double-blinded trial, European Heart Journal, Volume 41, Issue 36, 21 September 2020, Pages 3451–3458, https://doi.org/10.1093/eurheartj/ehaa541
8. Mathur, A., Sim, D.S., Choudry, F., Veerapen, J., Colicchia, M., Turlejski, T., Hussain, M., Hamshere, S., Locca, D., Rakhit, R., Crake, T., Kastrup, J., Agrawal, S., Jones, D. A., and Martin, J. (2022) Five-year follow-up of intracoronary autologous cell therapy in acute myocardial infarction: the REGENERATE-AMI trial. ESC Heart Failure, 9: 1152–1159 https://doi.org/10.1002/ehf2.13786
9. He X, Wang Q, Zhao Y, et al. Effect of Intramyocardial Grafting Collagen Scaffold With Mesenchymal Stromal Cells in Patients With Chronic Ischemic Heart Disease: A Randomized Clinical Trial. JAMA Netw Open. 2020;3(9):e2016236. doi:10.1001/jamanetworkopen.2020.16236
10. Qayyum, A.A., Frljak, S., Juhl, M., Poglajen, G., Zemljičl, G., Cerar, A., Litman, T., Ekblond, A., Haack-Sørensen, M., Højgaard, L. D., Kastrup, J., and Vrtovec, B. (2024) Mesenchymal stromal cells to treat patients with non-ischaemic heart failure: Results from SCIENCE II pilot study. ESC Heart Failure, 11: 3882–3891. https://doi.org/10.1002/ehf2.14925
11. Soetisna TW, Sukmawan R, Setianto B, et al. Combined transepicardial and transseptal implantation of autologous CD 133+ bone marrow cells during bypass grafting improves cardiac function in patients with low ejection fraction. J Card Surg. 2020; 35: 740–746. https://doi.org/10.1111/jocs.14454
12. Bozkurt B, Ahmad T, Alexander KM, Baker WL, Bosak K, Breathett K, Fonarow GC, Heidenreich P, Ho JE, Hsich E, Ibrahim NE, Jones LM, Khan SS, Khazanie P, Koelling T, Krumholz HM, Khush KK, Lee C, Morris AA, Page RL 2nd, Pandey A, Piano MR, Stehlik J, Stevenson LW, Teerlink JR, Vaduganathan M, Ziaeian B; Writing Committee Members. Heart Failure Epidemiology and Outcomes Statistics: A Report of the Heart Failure Society of America. J Card Fail. 2023 Oct;29(10):1412-1451. doi: 10.1016/j.cardfail.2023.07.006. Epub 2023 Sep 26. PMID: 37797885; PMCID: PMC10864030.
13. Liu, Z., Tang, Y., Lü, S., Zhou, J., Du, Z., Duan, C., Li, Z. and Wang, C. (2013), The tumourigenicity of iPS cells and their differentiated derivates. J. Cell. Mol. Med., 17: 782-791. https://doi.org/10.1111/jcmm.12062
14. Mazo, M., Planat-Bénard, V., Abizanda, G., Pelacho, B., Léobon, B., Gavira, J.J., Peñuelas, I., Cemborain, A., Pénicaud, L., Laharrague, P., Joffre, C., Boisson, M., Ecay, M., Collantes, M., Barba, J., Casteilla, L. and Prósper, F. (2008), Transplantation of adipose derived stromal cells is associated with functional improvement in a rat model of chronic myocardial infarction. European Journal of Heart Failure, 10: 454-462. https://doi.org/10.1016/j.ejheart.2008.03.017
15. Tang XL, Li Q, Rokosh G, Sanganalmath SK, Chen N, Ou Q, Stowers H, Hunt G, Bolli R. Long-Term Outcome of Administration of c-kit(POS) Cardiac Progenitor Cells After Acute Myocardial Infarction: Transplanted Cells Do not Become Cardiomyocytes, but Structural and Functional Improvement and Proliferation of Endogenous Cells Persist for at Least One Year. Circ Res. 2016 Apr 1;118(7):1091-105. doi: 10.1161/CIRCRESAHA.115.307647. Epub 2016 Feb 2. PMID: 26838790; PMCID: PMC4818175.Nair, N.,Gongora, E, Stem cell therapy in heart failure: Where do we stand today?,Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease,Volume 1866, Issue 4,2020,165489,ISSN 0925-4439,https://doi.org/10.1016/j.bbadis.2019.06.003.
16. Bhawnani N, Ethirajulu A, Alkasabera A, et al. (August 16, 2021) Effectiveness of Stem Cell Therapies in Improving Clinical Outcomes in Patients With Heart Failure. Cureus 13(8): e17236. doi: https://doi.org/10.7759/cureus.17236
17. Bhawnani N, Ethirajulu A, Alkasabera A, Onyali CB, Anim-Koranteng C, Shah HE, Mostafa JA. Effectiveness of Stem Cell Therapies in Improving Clinical Outcomes in Patients With Heart Failure. Cureus. 2021 Aug 16;13(8):e17236. doi: https://doi.org/10.7759/cureus.17236. PMID: 34540463; PMCID: PMC8447853.
18. Crespo-Leiro MG, Metra M, Lund LH, Milicic D, Costanzo MR, Filippatos G, Gustafsson F, Tsui S, Barge-Caballero E, De Jonge N, Frigerio M, Hamdan R, Hasin T, Hülsmann M, Nalbantgil S, Potena L, Bauersachs J, Gkouziouta A, Ruhparwar A, Ristic AD, Straburzynska-Migaj E, McDonagh T, Seferovic P, Ruschitzka F. Advanced heart failure: a position statement of the Heart Failure Association of the European Society of Cardiology. Eur J Heart Fail. 2018 Nov;20(11):1505-1535. doi: https://doi.org/10.1002/ejhf.1236. Epub 2018 Jul 17. PMID: 29806100.
19. Crespo-Leiro MG, Metra M, Lund LH, Milicic D, Costanzo MR, Filippatos G, Gustafsson F, Tsui S, Barge-Caballero E, De Jonge N, Frigerio M, Hamdan R, Hasin T, Hülsmann M, Nalbantgil S, Potena L, Bauersachs J, Gkouziouta A, Ruhparwar A, Ristic AD, Straburzynska-Migaj E, McDonagh T, Seferovic P, Ruschitzka F. Advanced heart failure: a position statement of the Heart Failure Association of the European Society of Cardiology. Eur J Heart Fail. 2018 Nov;20(11):1505-1535. doi: https://doi.org/10.1002/ejhf.1236. Epub 2018 Jul 17. PMID: 29806100.
20. Tsao CW, Aday AW, Almarzooq ZI, Alonso A, Beaton AZ, Bittencourt MS, Boehme AK, Buxton AE, Carson AP, Commodore-Mensah Y, Elkind MSV, Evenson KR, Eze-Nliam C, Ferguson JF, Generoso G, Ho JE, Kalani R, Khan SS, Kissela BM, Knutson KL, Levine DA, Lewis TT, Liu J, Loop MS, Ma J, Mussolino ME, Navaneethan SD, Perak AM, Poudel R, Rezk-Hanna M, Roth GA, Schroeder EB, Shah SH, Thacker EL, VanWagner LB, Virani SS, Voecks JH, Wang NY, Yaffe K, Martin SS. Heart Disease and Stroke Statistics-2022 Update: A Report From the American Heart Association. Circulation. 2022 Feb 22;145(8):e153-e639. doi: https://doi.org/10.1161/CIR.0000000000001052. Epub 2022 Jan 26. Erratum in: Circulation. 2022 Sep 6;146(10):e141. doi: 10.1161/CIR.0000000000001074. PMID: 35078371.
21. Takahashi, K., Yamanaka, S.; Induction of Pluripotent Stem Cells from Mouse Embryonic and Adult Fibroblast Cultures by Defined Factors,Cell,Volume 126, Issue 4,2006,Pages 663-676,ISSN 0092-8674,https://doi.org/10.1016/j.cell.2006.07.024.
22. Takahashi, K., Tanabe, K. , Ohnuki, M. , Narita, M. , Ichisaka, T., Tomoda, K., Yamanaka, S. , Induction of Pluripotent Stem Cells from Adult Human Fibroblasts by Defined Factors,Cell,Volume 131, Issue 5,2007,Pages 861-872,ISSN 0092-8674,https://doi.org/10.1016/j.cell.2007.11.019.
23. Ye L, Chang YH, Xiong Q, Zhang P, Zhang L, Somasundaram P, Lepley M, Swingen C, Su L, Wendel JS, Guo J, Jang A, Rosenbush D, Greder L, Dutton JR, Zhang J, Kamp TJ, Kaufman DS, Ge Y, Zhang J. Cardiac repair in a porcine model of acute myocardial infarction with human induced pluripotent stem cell-derived cardiovascular cells. Cell Stem Cell. 2014 Dec 4;15(6):750-61. doi: https://doi.org/10.1016/j.stem.2014.11.009. Erratum in: Cell Stem Cell. 2015 Jan 8;16(1):102. PMID: 25479750; PMCID: PMC4275050.
24. Tehzeeb J, Manzoor A, Ahmed MM. Is Stem Cell Therapy an Answer to Heart Failure: A Literature Search. Cureus. 2019 Oct 22;11(10):e5959. doi: https://doi.org/10.7759/cureus.5959. PMID: 31803548; PMCID: PMC6874291.
25. Rheault-Henry M, White I, Grover D, Atoui R. Stem cell therapy for heart failure: Medical breakthrough, or dead end? World J Stem Cells 2021; 13(4): 236-259 [PMID: PMC8080540 DOI: https://doi.org/10.4252/wjsc.v13.i4.236
26. Menasché P. Cell therapy trials for heart regeneration - lessons learned and future directions. Nat Rev Cardiol. 2018 Nov;15(11):659-671. doi: https://doi.org/10.1038/s41569-018-0013-0. PMID: 29743563.
27. Bruyneel AA, Sehgal A, Malandraki-Miller S, Carr C. Stem Cell Therapy for the Heart: Blind Alley or Magic Bullet? J Cardiovasc Transl Res. 2016 Dec;9(5-6):405-418. doi: https://doi.org/10.1007/s12265-016-9708-y. Epub 2016 Aug 19. PMID: 27542008; PMCID: PMC5153828.
28. Nakamura K, Murry CE. Function Follows Form - A Review of Cardiac Cell Therapy. Circ J. 2019 Nov 25;83(12):2399-2412. doi: https://doi.org/10.1253/circj.CJ-19-0567. Epub 2019 Nov 13. PMID: 31723070; PMCID: PMC7002039.
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Copyright (c) 2025 Igor Zydlewski, Małgorzata Blecharczyk, Paweł Jakubiec, Maciej Kosiński, Martyna Mrozek, Alicja Nowik, Martyna Pacanowska, Marcin Sękulski

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