CHAPTER


DOI :10.26650/B/LS17LS30.2025.038.015   IUP :10.26650/B/LS17LS30.2025.038.015    Full Text (PDF)

The Immunogenicity of Stem Cell-based Therapy for Cardiovascular Disease

Hilal ŞentürkMehmet KaracanEvrim Kömürcü Bayrak

Cell-based therapy approaches for cardiovascular diseases (CVDs) causing heart failure (HF) have become an interesting topic in recent years. In these studies, stem cells often play a role in heart repair in two different ways. The first technique entails the generation of fresh cardiomyocytes to replenish lost heart tissue. This mechanism functions in accordance with the differentiation of stem or progenitor cells. The second application is paracrine stimulation. The best types of stem cells not only perfuse tissue but also discharge paracrine chemicals and extracellular vesicles that control the healing process, affect the host immune system, and aid in cell survival and restoration of heart function. This chapter presents preclinical and clinical research, and the processes and stem cell types that promote heart repair in cardiovascular illnesses.



References

  • 1. Tsao CW, Aday AW, Almarzooq ZI, Anderson CAM, Arora P, Avery CL, et al. Heart disease and stroke statistics-2023 update: a report from the American Heart Association. Circulation. 2023;147(8):e93-621. google scholar
  • 2. Cuijpers P, Noma H, Karyotaki E, Vinkers CH, Cipriani A, Furukawa TA. A network meta-analysis of the effects of psychotherapies, pharmacotherapies and their combination in the treatment of adult depression. World Psychiatry. 2020;19(1):92-107. google scholar
  • 3. Salerno N, Salerno L, Marino F, Scalise M, Chiefalo A, Panuccio G, et al. Myocardial regeneration protocols towards the routine clinical scenario: An unseemly path from bench to bedside. EClinicalMedicine. 2022;50:101530. google scholar
  • 4. Schwartz PJ, Ackerman MJ, Antzelevitch C, Bezzina CR, Borggrefe M, Cuneo BF, et al. Inherited cardiac arrhythmias. Nat Rev Dis Primers. 2020;16;6(1):58. google scholar
  • 5. Fernandez-Aviles F, Sanz-Ruiz R, Climent AM, Badimon L, Bolli R, Charron D, et al. Global position paper on cardiovascular regenerative medicine [published correction appears in Eur Heart J. 2018 May 14;39(19):1723]. Eur Heart J. 2017;38(33):2532-46. google scholar
  • 6. Rurik JG, Aghajanian H, Epstein JA. Immune cells and immunotherapy for cardiac injury and repair. Circ Res. 2021;128(11):1766-79. google scholar
  • 7. Orlic D, Kajstura J, Chimenti S, Jakoniuk I, Anderson SM, Li B, et al. Bone marrow cells regenerate infarcted myocardium. Nature. 2001;410(6829):701-5. google scholar
  • 8. Stamm C, Westphal B, Kleine H-D, Petzsch M, Kittner C, Klinge H, et al. Autologous bone-marrow stem-cell transplantation for myocardial regeneration. The Lancet. 2003;361(9351):45-6. google scholar
  • 9. Evans MJ, Kaufman, MH. Establishment in culture of pluripotential cells from mouse embryos. Nature. 1981;292(5819):154-6. google scholar
  • 10. Thomson JA. Embryonic stem cell lines derived from human blastocysts. Science. 1998;282(5391):1145-7. google scholar
  • 11. Talkhabi M, Aghdami N, Baharvand H. Human cardiomyocyte generation from pluripotent stem cells: A state-of-art. Life Sci.2016;145:98-113. google scholar
  • 12. Veerman CC, Kosmidis G, Mummery CL, Casini S, Verkerk AO, Bellin M. Immaturity of human stem-cell derived cardiomyocytes in culture: fatal flaw or soluble problem? Stem Cells Dev. 2015;24(9):1035-52. google scholar
  • 13. Min JY, Yang Y, Converso KL, Liu L, Huang Q, Morgan JP, et al. Transplantation of embryonic stem cells improves cardiac function in postinfarcted rats. J Appl Physiol (1985). 2002;92(1):288-96. google scholar
  • 14. Behfar A, Zingman LV, Hodgson DM, Rauzier JM, Kane GC, Terzic A, et al. Stem cell differentiation requires a paracrine pathway in the heart. FASEB J. 2002;16(12):1558-66. google scholar
  • 15. Jain, K.K. Ethical and regulatory aspects of embryonic stem cell research. Expert Opin Biol Ther. 2005;5(2):153-62. google scholar
  • 16. Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell. 2006;126(4):663-76. google scholar
  • 17. Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, et al. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell. 2007;131(5):861-72. google scholar
  • 18. Ptaszek LM, Mansour M, Ruskin JN, Chien KR. Towards regenerative therapy for cardiac disease. Lancet. 2012;379(9819):933-42. google scholar
  • 19. Yu H, Lu K, Zhu J, Wang J. Stem cell therapy for ischemic heart diseases. Br Med Bull. 2017;121(1):135-54. google scholar
  • 20. Masumoto H, Ikuno T, Takeda M, Fukushima H, Marui A, Katayama S, et al. Human iPS cell-engineered cardiac tissue sheets with cardiomyocytes and vascular cells for cardiac regeneration. Sci Rep. 2014;4:6716. google scholar
  • 21. Kawamura M, Miyagawa S, Miki K, Saito A, Fukushima S, Higuchi T, et al. Feasibility, safety, and therapeutic efficacy of human induced pluripotent stem cell-derived cardiomyocyte sheets in a porcine ischemic cardiomyopathy model. Circulation. 2012;126(11 Suppl 1):S29-37. google scholar
  • 22. Yamashita JK. ES and iPS cell research for cardiovascular regeneration. Exp Cell Res. 2010;316(16):2555-59. google scholar
  • 23. Yoshida Y, Yamanaka S. iPS cells: A source of cardiac regeneration. J Mol Cell Cardiol. 2011;50(2):327-32. google scholar
  • 24. Dezawa M, Kanno H, Hoshino M, Cho H, Matsumoto N, Itokazu Y, et al. Specific induction of neuronal cells from bone marrow stromal cells and application for autologous transplantation. J Clin Invest. 2004;113:1701-10. google scholar
  • 25. Elnakish MT, Hassan F, Dakhlallah D, Marsh CB, Alhaider IA, Khan M. Mesenchymal stem cells for cardiac regeneration: Translation to bedside reality. Stem Cells Int. 2012;2012:646038. google scholar
  • 26. Woodbury D, Schwarz EJ, Prockop DJ, Black IB. Adult rat and human bone marrow stromal cells differentiate into neurons. J Neurosci Res. 2000;61(4):364-70. google scholar
  • 27. Mebarki M, Abadie C, Larghero J, Cras A. Human umbilical cord-derived mesenchymal stem/stromal cells: A promising candidate for the development of advanced therapy medicinal products. Stem Cell Res Ther. 2021;26;12(1):152. google scholar
  • 28. Guo Y, Yu Y, Hu S, Chen Y, Shen Z. The therapeutic potential of mesenchymal stem cells for cardiovascular diseases. Cell Death Dis. 2020;11;11(5):349. google scholar
  • 29. Belien H, Evens L, Hendrikx M, Bito V, Bronckaers A. Combining stem cells in myocardial infarction: The road to superior repair? Med Res Rev. 2022;42(1):343-73. google scholar
  • 30. Kinnaird T, Stabile E, Burnett MS, Lee CW, Barr S, Fuchs S, et al. Marrow-derived stromal cells express genes encoding a broad spectrum of arteriogenic cytokines and promote in vitro and in vivo arteriogenesis through paracrine mechanisms. Circ Res. 2004;94(5):678-85. google scholar
  • 31. Yushkov BG, Sarapultsev AP. Stem cells and cardiac arrhythmias. Gen Physiol Biophys. 2022;41(6):483-98. google scholar
  • 32. Bergmann O, Bhardwaj RD, Bernard S, Zdunek S, Barnabe—Heider F, Walsh S, et al. Evidence for cardiomyocyte renewal in humans. Science. 2009;324(5923):98-102. google scholar
  • 33. Hsieh PC, Segers VF, Davis ME, MacGillivray C, Gannon J, Molkentin JD, et al. Evidence from a genetic fate-mapping study that stem cells refresh adult mammalian cardiomyocytes after injury. Nat Med. 2007;13(8):970-74. google scholar
  • 34. Malliaras K, Zhang Y, Seinfeld J, Galang G, Tseliou E, Cheng K, et al. Cardiomyocyte proliferation and progenitor cell recruitment underlie therapeutic regeneration after myocardial infarction in the adult mouse heart. EMBO Mol Med. 2013;5(2):191-209. google scholar
  • 35. Senyo SE, Steinhauser ML, Pizzimenti CL, Yang VK, Cai L, Wang M, et al. Mammalian heart renewal by pre-existing cardiomyocytes. Nature. 2013;493(7432):433-6. google scholar
  • 36. Beltrami AP, Barlucchi L, Torella D, Baker M, Limana F, Chimenti S, et al. Adult cardiac stem cells are multipotent and support myocardial regeneration. Cell. 2003;114(6):763-76. google scholar
  • 37. Malliaras K, Li TS, Luthringer D, Terrovitis J, Cheng K, Chakravarty T, et al. Safety and efficacy of allogeneic cell therapy in infarcted rats transplanted with mismatched cardiosphere-derived cells. Circulation. 2012;125:100-12. google scholar
  • 38. Ostovaneh MR, Makkar RR, Ambale-Venkatesh B, Ascheim D, Chakravarty T, Henry TD, et al. Effect of cardiosphere-derived cells on segmental myocardial function after myocardial infarction: ALLSTAR randomised clinical trial. Open Heart. 2021;8(2):e001614. google scholar
  • 39. Asahara T, Murohara T, Sullivan A, Silver M, van der Zee R, Li T, et al. Isolation of putative progenitor endothelial cells for angiogenesis. Science. 1997;275(5302):964-7. google scholar
  • 40. Vega FM, Gautier V, Fernandez-Ponce CM, Extremera MJ, Altelaar AFM, Millan J, et al. The atheroma plaque secretome stimulates the mobilization of endothelial progenitor cells ex vivo. J Mol Cell Cardiol. 2017;105:12-23. google scholar
  • 41. Chen CW, Wang LL, Zaman S, Gordon J, Arisi MF, Venkataraman CM, et al. Sustained release of endothelial progenitor cell-derived extracellular vesicles from shear-thinning hydrogels improves angiogenesis and promotes function after myocardial infarction. Cardiovasc Res. 2018;114(7):1029-40. google scholar
  • 42. Dixon JA, Spinale FG. Large animal models of heart failure: A critical link in the translation of basic science to clinical practice. Circ Heart Fail. 2009;2:262-71. google scholar
  • 43. Arminan A, Gandıa C, Garcla-Verdugo JM, Lledo E, Trigueros C, Ruiz-Saurı A, et al. Mesenchymal stem cells provide better results than hematopoietic precursors for the treatment of myocardial infarction. J Am Coll Cardiol. 2010;55(20):2244-53. google scholar
  • 44. Shake JG, Gruber PJ, Baumgartner WA, Senechal G, Meyers J, Redmond JM, et al. Mesenchymal stem cell implantation in a swine myocardial infarct model: Engraftment and functional effects. Ann Thorac Surg. 2002;73:1919-25. google scholar
  • 45. Silva GV, Litovsky S, Assad JA, Sousa AL, Martin BJ, Vela D, et al. Mesenchymal stem cells differentiate into an endothelial phenotype, enhance vascular density, and improve heart function in a canine chronic ischemia model. Circulation. 2005;111(2):150-6. google scholar
  • 46. Chen SL, Fang WW, Ye F, Liu YH, Qian J, Shan SJ, et al. Effect on left ventricular function of intracoronary transplantation of autologous bone marrow mesenchymal stem cell in patients with acute myocardial infarction. Am J Cardiol. 2004;94(1):92-5. google scholar
  • 47. Guijarro D, Lebrin M, Lairez O, Bourin P, Piriou N, Pozzo J, et al. Intramyocardial transplantation of mesenchymal stromal cells for chronic myocardial ischemia and impaired left ventricular function: results of the MESAMI 1 pilot trial. Int J Cardiol. 2016;209:258-65. google scholar
  • 48. Tang YL, Zhao Q, Zhang YC, Cheng L, Liu M, Shi J, et al. Autologous mesenchymal stem cell transplantation induces VEGF and neovascularization in ischemic myocardium. Regul Pept. 2004;117:3-10. google scholar
  • 49. Mu Y, Cao G, Zeng Q, Li Y. Transplantation of induced bone marrow mesenchymal stem cells improves the cardiac function of rabbits with dilated cardiomyopathy via upregulation of vascular endothelial growth factor and its receptors. Exp Biol Med (Maywood). 2011;236:1100-7. google scholar
  • 50. Nagaya N, Kangawa K, Itoh T, Iwase T, Murakami S, Miyahara Y, et al. Transplantation of mesenchymal stem cells improves cardiac function in a rat model of dilated cardiomyopathy. Circulation. 2005;112:1128-35. google scholar
  • 51. Williams AR, Hatzistergos KE, Addicott B, McCall F, Carvalho D, Suncion VY, et al. Enhanced effect of combining human cardiac stem cells and bone marrow mesenchymal stem cells to reduce infarct size and restore cardiac function after myocardial infarction. Circulation. 2013;127:213-23. google scholar
  • 52. Hatzistergos KE, Quevedo H, Öskouei BN, Hu Q, Feigenbaum GS, Margitich IS, et al. Bone marrow mesenchymal stem cells stimulate cardiac stem cell proliferation and differentiation. Circ Res. 2010;107:913-22. google scholar
  • 53. Quevedo HC, Hatzistergos KE, Öskouei BN, Feigenbaum GS, Rodriguez JE, Valdes D, et al. Allogeneic mesenchymal stem cells restore cardiac function in chronic ischemic cardiomyopathy via trilineage differentiating capacity. Proc Natl Acad Sci JSA. 2009;106:14022-7. google scholar
  • 54. Ding R, Jiang X, Ha Y, Wang Z, Guo J, Jiang H, et al. Activation of Notch1 signalling promotes multi-lineage differentiation of c-Kit(PÖS)/NKX2.5(PÖS) bone marrow stem cells: Implication in stem cell translational medicine. Stem Cell Res Ther. 2015;6(1):91. google scholar
  • 55. Shen X, Pan B, Zhou H, Liu L, Lv T, Zhu J, et al. Differentiation of mesenchymal stem cells into cardiomyocytes is regulated by miRNA-1-2 via WNT signaling pathway. J Biomed Sci. 2017;10;24(1):29. google scholar
  • 56. Houtgraaf JH, de Jong R, Kazemi K, de Groot D, van der Spoel TI, Arslan F, et al. Intracoronary infusion of allogeneic mesenchymal precursor cells directly after experimental acute myocardial infarction reduces infarct size, abrogates adverse remodeling, and improves cardiac function. Circ Res. 2013;113:153-66. google scholar
  • 57. Cheng Y, Yi G, Conditt GB, Sheehy A, Kolodgie FD, Tellez A, et al. Catheter-based endomyocardial delivery of mesenchymal precursor cells using 3D echo guidance improves cardiac function in a chronic myocardial injury ovine model. Cell Transplant. 2013;22(12):2299-309. google scholar
  • 58. Gong C, Chang L, Sun X, Qi Y, Huang R, Chen K, et al. Infusion of two-dose mesenchymal stem cells is more effective than a single dose in a dilated cardiomyopathy rat model by upregulating indoleamine 2,3-dioxygenase expression. Stem Cell Res Ther. 2022;13(1):409. google scholar
  • 59. Rasmussen JG, Frobert O, Holst-Hansen C, Kastrup J, Baandrup U, Zachar V, et al. Comparison of human adipose-derived stem cells and bone marrow-derived stem cells in a myocardial infarction model. Cell Transplant. 2014;23:195-206. google scholar
  • 60. Leobon B, Roncalli J, Joffre C, Mazo M, Boisson M, Barreau C, et al. Adipose-derived cardiomyogenic cells: In vitro expansion and functional improvement in a mouse model of myocardial infarction. Cardiovasc Res. 2009;83:757-67. google scholar
  • 61. Bobi J, Solanes N, Fernandez-Jimenez R, Galan-Arriola C, Dantas AP, Fernandez-Friera L, et al. Intracoronary administration of allogeneic adipose tissue-derived mesenchymal stem cells improves myocardial perfusion but not left ventricle function, in a translational model of acute myocardial infarction. J Am Heart Assoc. 2017;3;6(5):e005771. google scholar
  • 62. Santos Nascimento D, Mosqueira D, Sousa LM, Teixeira M, Filipe M, Resende TP, et al. Human umbilical cord tissue-derived mesenchymal stromal cells attenuate remodeling after myocardial infarction by proangiogenic, antiapoptotic, and endogenous cell-activation mechanisms. Stem Cell Res Ther. 2014;10;5(1):5. google scholar
  • 63. Zhang W, Liu XC, Yang L, Zhu DL, Zhang YD, Chen Y, et al. Wharton’s jelly-derived mesenchymal stem cells promote myocardial regeneration and cardiac repair after miniswine acute myocardial infarction. Coron Artery Dis. 2013;24:549-58. google scholar
  • 64. Kunisada T, Yoshida H, Yamazaki H, Miyamoto A, Hemmi H, Nishimura E, et al. Transgene expression of steel factor in the basal layer of epidermis promotes survival, proliferation, differentiation and migration of melanocyte precursors. Development. 1998;125:2915-23. google scholar
  • 65. Oskouei BN, Lamirault G, Joseph C, Treuer AV, Landa S, Da Silva J, et al. Increased potency of cardiac stem cells compared with bone marrow mesenchymal stem cells in cardiac repair. Stem Cells Translational Medicine. 2012;1:116-24. google scholar
  • 66. Bolli R, Tang XL, Sanganalmath SK, Rimoldi O, Mosna F, Abdel-Latif A, et al. Intracoronary delivery of autologous cardiac stem cells improves cardiac function in a porcine model of chronic ischemic cardiomyopathy. Circulation. 2013;128:122-31. google scholar
  • 67. Zwetsloot PP, Vegh AM, Jansen of Lorkeers SJ, van Hout GP, Currie GL, Sena ES, et al. Cardiac stem cell treatment in myocardial infarction: A systematic review and meta-analysis of preclinical studies. Circ Res. 2016;15;118(8):1223-32. google scholar
  • 68. Fanton Y, Houbrechts C, Willems L, Daniels A, Linsen L, Ratajczak J, et al. Cardiac atrial appendage stem cells promote angiogenesis in vitro and in vivo. JMol Cell Cardiol. 2016;97:235-44. google scholar
  • 69. Fanton Y, Robic B, Rummens JL, Daniels A, Windmolders S, Willems L, et al. Cardiac atrial appendage stem cells engraft and differentiate into cardiomyocytes in vivo: A new tool for cardiac repair after MI. Int J Cardiol. 2015;201:10-19. google scholar
  • 70. Koninckx R, Daniels A, Windmolders S, Mees U, Macianskiene R, Mubagwa K, et al. The cardiac atrial appendage stem cell: a new and promising candidate for myocardial repair. Cardiovasc Res. 2013;97(3):413-23. google scholar
  • 71. Grigorian-Shamagian L, Liu W, Fereydooni S, Middleton RC, Valle J, Cho JH, et al. Cardiac and systemic rejuvenation after cardiosphere-derived cell therapy in senescent rats. Eur Heart J. 2017;38:2957-67. google scholar
  • 72. Kobayashi T, Hamano K, Li TS, Katoh T, Kobayashi S, Matsuzaki M, et al. Enhancement of angiogenesis by the implantation of self-bone marrow cells in a rat ischemic heart model. J Surg Res. 2000;89:189-95. google scholar
  • 73. Mathieu M, Bartunek J, El Oumeiri B, Touihri K, Hadad I, Thoma P, et al. Cell therapy with autologous bone marrow mononuclear stem cells is associated with superior cardiac recovery compared with use of nonmodified mesenchymal stem cells in a canine model of chronic myocardial infarction. J Thorac Cardiovasc Surg. 2009;138:646-53. google scholar
  • 74. Bel A, Messas E, Agbulut O, Richard P, Samuel JL, Bruneval P, et al. Transplantation of autologous fresh bone marrow into infarcted myocardium: a word of caution. Circulation. 2003;108 Suppl 1:II247-52. google scholar
  • 75. Kawamoto A, Gwon HC, Iwaguro H, Yamaguchi JI, Jchida S, Masuda H, et al. Therapeutic potential of ex vivo expanded endothelial progenitor cells for myocardial ischemia. Circulation. 2001;103(5):634-7. google scholar
  • 76. Kocher AA, Schuster MD, Szabolcs MJ, Takuma S, Burkhoff D, Wang J, et al. Neovascularization of ischemic myocardium by human bone-marrow-derived angioblasts prevents cardiomyocyte apoptosis, reduces remodeling and improves cardiac function. Nat Med. 2001;7:430-6. google scholar
  • 77. Thal MA, Krishnamurthy P, Mackie AR, Hoxha E, Lambers E, Verma S, et al. Enhanced angiogenic and cardiomyocyte differentiation capacity of epigenetically reprogrammed mouse and human endothelial progenitor cells augments their efficacy for ischemic myocardial repair. Circ Res. 2012;111:180-90. google scholar
  • 78. Kupatt C, Hinkel R, Lamparter M, von Briihl ML, Pohl T, Horstkotte J, et al. Retroinfusion of embryonic endothelial progenitor cells attenuates ischemia reperfusion injiry in pigs: Role of phosphatidylinositol 3-kinase/AKT kinase. Circilation. 2005;112(9 sippl):I117-I122. google scholar
  • 79. Shintani S, Mirohara T, Ikeda H, Ueno T, Honma T, Katoh A, et al. Mobilization of endothelial progenitor cells in patients with acite myocardial infarction. Circilation. 2001;103(23):2776-9. google scholar
  • 80. Valgimigli M, Rigolin GM, Ficili A, Porta MD, Soikhomovskaia O, Malagitti P, et al. CD34+ and endothelial progenitor cells in patients with variois degrees of congestive heart failire. Circilation. 2004;110(10):1209-12. google scholar
  • 81. Citro L, Naidi S, Hassan F, Kippisamy ML, Kippisamy P, Angelos MG, et al. Comparison of himan indiced pliripotent stem-cell derived cardiomyocytes with himan mesenchymal stem cells following acite myocardial infarction. PLoS One. 2014;9(12):e116281. google scholar
  • 82. Zhang L, Gio J, Zhang P, Xiong Q, Wi SC, Xia L, et al. Derivation and high engraftment of patient-specific cardiomyocyte sheet ising indiced pliripotent stem cells generated from adilt cardiac fibroblast. Circ Heart Fail. 2015;8(1):156-66. google scholar
  • 83. Ye L, Chang YH, Xiong Q, Zhang P, Zhang L, Somasindaram P, et al. Cardiac repair in a porcine model of acite myocardial infarction with himan indiced pliripotent stem cell-derived cardiovascilar cells [piblished correction appears in Cell Stem Cell. 2015;8;16(1):102]. Cell Stem Cell. 2014;15(6):750-61. google scholar
  • 84. Carpenter L, Carr C, Yang CT, Stickey DJ, Clarke K, Watt SM. Efficient differentiation of himan indiced pliripotent stem cells generates cardiac cells that provide protection following myocardial infarction in the rat. Stem Cells Dev. 2012;21(6):977-86. google scholar
  • 85. Mairitz C, Martens A, Rojas SV, Schnick T, Rathert C, Schecker N, et al. Indiced pliripotent stem cell (iPSC)-derived Flk-1 progenitor cells engraft, differentiate, and improve heart finction in a moise model of acite myocardial infarction. Eir Heart J. 2011;32(21):2634-41. google scholar
  • 86. Riegler J, Tiburcy M, Ebert A, Tzatzalos E, Raaz U, Abilez OJ, et al. Human engineered heart muscles engraft and survive long term in a rodent myocardial infarction model. Circ Res. 2015;117(8):720-30. google scholar
  • 87. Shiba Y, Fernandes S, Zhu WZ, Filice D, Muskheli V, Kim J, et al. Human ES-cell-derived cardiomyocytes electrically couple and suppress arrhythmias in injured hearts. Nature. 2012;489(7415):322-5. google scholar
  • 88. Chong JJ, Yang X, Don CW, Minami E, Liu YW, Weyers JJ, et al. Human embryonic-stem-cell-derived cardiomyocytes regenerate non-human primate hearts. Nature. 2014;510(7504):273-7. google scholar
  • 89. Templin C, Zweigerdt R, Schwanke K, Olmer R, Ghadri JR, Emmert MY, et al. Transplantation and tracking of human-induced pluripotent stem cells in a pig model of myocardial infarction: assessment of cell survival, engraftment, and distribution by hybrid single photon emission computed tomography/computed tomography of sodium iodide symporter transgene expression. Circulation. 2012;126:430-9. google scholar
  • 90. Zhu K, Wu Q, Ni C, Zhang P, Zhong Z, Wu Y, et al. Lack of remuscularization following transplantation of human embryonic stem cell-derived cardiovascular progenitor cells in infarcted nonhuman primates. Circ Res. 2018;30;122(7):958-69. google scholar
  • 91. Eugenin E, Camporesi E, Peracchia C. Direct cell-cell communication via membrane pores, gap junction channels, and tunneling nanotubes: Medical relevance of mitochondrial exchange. Int J Mol Sci. 2022; 23(11):6133. google scholar
  • 92. Poynter JA, Herrmann JL, Manukyan MC, Wang Y, Abarbanell AM, Weil BR, et al. Intracoronary mesenchymal stem cells promote post- ischemic myocardial functional recovery, decrease inflammation, and reduce apoptosis via a signal trans- ducer and activator of transcription 3 mechanism. J Am Coll Surg. 2011;213:253-60. google scholar
  • 93. Kanelidis AJ, Premer C, Lopez J, Balkan W, Hare JM. Route of delivery modulates the efficacy of mesenchymal stem cell therapy for myocardial infarction: A meta-analysis of preclinical studies and clinical trials. Circ Res. 2017;120(7):1139-50. google scholar
  • 94. Schachinger V, Assmus B, Britten MB, Honold J, Lehmann R, Teupe C, et al. Transplantation of progenitor cells and regeneration enhancement in acute myocardial infarction: Final one-year results of the TOPCARE-AMI Trial. J Am Coll Cardiol. 2004;44(8):1690-9. google scholar
  • 95. Chong MS, Ng WK, Chan JK. Concise review: Endothelial progenitor cells in regenerative medicine: Applications and challenges. Stem Cells Transl Med. 2016;5:530-8. google scholar
  • 96. Quyyumi AA, Vasquez A, Kereiakes DJ, Klapholz M, Schaer GL, Abdel-Latif A, et al. PreSERVE-AMI: A randomized, double-blind, placebo-controlled clinical trial of intracoronary administration of autologous CD34+ cells in patients with left ventricular dysfunction post STEMI. Circ Res. 2017;120(2):324-31. google scholar
  • 97. Gao LR, Chen Y, Zhang NK, Yang XL, Liu HL, Wang ZG, Yetal. Intracoronary infusion of Wharton’s jelly-derived mesenchymal stem cells in acute myocardial infarction: Double-blind, randomized controlled trial. BMC Med. 2015;13:162. google scholar
  • 98. Fernandez-Aviles F, Sanz-Ruiz R, Bogaert J, Casado Plasencia A, Gilaberte I, Belmans A, et al. Safety and efficacy of intracoronary infusion of allogeneic human cardiac stem cells in patients with ST-segment elevation myocardial infarction and left ventricular dysfunction. Circ Res. 2018;123(5):579-89. google scholar
  • 99. Perin EC, Dohmann HF, Borojevic R, Silva SA, Sousa AL, Mesquita CT, et al. Transendocardial, autologous bone marrow cell transplantation for severe, chronic ischemic heart failure. Circulation. 2003;107(18):2294-02. google scholar
  • 100. Assmus B, Fischer-Rasokat U, Honold J, Seeger FH, Fichtlscherer S, Tonn T, et al. Transcoronary transplantation of functionally competent BMCs is associated with a decrease in natriuretic peptide serum levels and improved survival of patients with chronic postinfarction heart failure: results of the TOPCARE-CHD Registry. Circ Res. 2007;100(8):1234-41. google scholar
  • 101. Perin EC, Willerson JT, Pepine CJ, Henry TD, Ellis SG, Zhao DX, et al. Effect of transendocardial delivery of autologous bone marrow mononuclear cells on functional capacity, left ventricular function, and perfusion in chronic heart failure: The FOCUS-CCTRN trial. JAMA. 2012;307(16):1717-26. google scholar
  • 102. Makkar RR, Smith RR, Cheng K, Malliaras K, Thomson LE, Berman D, et al. Intracoronary cardiosphere-derived cells for heart regeneration after myocardial infarction (CADUCEUS): A prospective, randomised phase 1 trial. Lancet. 2012;379(9819):895-904. google scholar
  • 103. Chakravarty T, Makkar RR, Ascheim DD, Traverse JH, Schatz R, DeMaria A, et al. Allogeneic heart stem cells to achieve myocardial regeneration (ALLSTAR) trial: Rationale and design. Cell Transplant. 2017;26(2):205-14. google scholar
  • 104. Fischer-Rasokat U, Assmus B, Seeger FH, Honold J, Leistner D, Fichtlscherer S, et al. A pilot trial to assess potential effects of selective intracoronary bone marrow-derived progenitor cell infusion in patients with nonischemic dilated cardiomyopathy: Final 1-year results of the transplantation of progenitor cells and functional regeneration enhancement pilot trial in patients with nonischemic dilated cardiomyopathy. Circ Heart Fail. 2009;2(5):417-23. google scholar
  • 105. Martino H, Brofman P, Greco O, Bueno R, Bodanese L, Clausell N, et al. Multicentre, randomized, double-blind trial of intracoronary autologous mononuclear bone marrow cell injection in non-ischaemic dilated cardiomyopathy (the dilated cardiomyopathy arm of the MiHeart study). Eur Heart J. 2015;36(42):2898-904. google scholar
  • 106. Banerjee MN, Bolli R, Hare JM. Clinical studies of cell therapy in cardiovascular medicine: recent developments and future directions. Circ Res. 2018;123(2):266-87. google scholar
  • 107. Vrtovec B, Poglajen G, Lezaic L, Sever M, Domanovic D, Cernelc P, et al. Effects of intracoronary CD34+ stem cell transplantation in non- ischemic dilated cardiomyopathy patients: 5-year follow-up. Circ Res. 2013;112(1):165-73. google scholar
  • 108. Hare JM, Fishman JE, Gerstenblith G, DiFede Velazquez DL, Zambrano JP, et al. Comparison of allogeneic vs autologous bone marrow-derived mesenchymal stem cells delivered by transendocardial injection in patients with ischemic cardiomyopathy: The POSEIDON randomized trial. JAMA. 2012;308(22):2369-79. google scholar
  • 109. Heldman AW, DiFede DL, Fishman JE, Zambrano JP, Trachtenberg BH, Karantalis V, et al. Transendocardial mesenchymal stem cells and mononuclear bone marrow cells for ischemic cardiomyopathy: The TAC-HFT randomized trial. JAMA. 2014;311(1):62-73. google scholar
  • 110. Williams AR, Hatzistergos KE, Addicott B, McCall F, Carvalho D, Suncion V, et al. Enhanced effect of combining human cardiac stem cells and bone marrow mesenchymal stem cells to reduce infarct size and to restore cardiac function after myocardial infarction. Circulation. 2013;127(2):213-23. google scholar
  • 111. Chugh AR, Beache GM, Loughran JH, Mewton N, Elmore JB, Kajstura J, et al. Administration of cardiac stem cells in patients with ischemic cardiomyopathy: The SCIPIO trial: Surgical aspects and interim analysis of myocardial function and viability by magnetic resonance. Circulation. 2012;126 (11 Suppl 1):54-64. google scholar
  • 112. Karantalis V, Suncion-Loescher VY, Bagno L, Golpanian S, Wolf A, Sanina C, et al. Synergistic effects of combined cell therapy for chronic ischemic cardiomyopathy. J Am Coll Cardiol. 2015;66(18):1990-9. google scholar
  • 113. Natsumeda M, Florea V, Rieger AC, Tompkins BA, Banerjee MN, Golpanian S, et al. A combination of allogeneic stem cells promotes cardiac regeneration. J Am Coll Cardiol. 2017;14;70(20):2504-15. google scholar
  • 114. Jansen of Lorkeers SJ, Eding JE, Vesterinen HM, van der Spoel TI, Sena ES, Duckers HJ, et al. Similar effect of autologous and allogeneic cell therapy for ischemic heart disease: Systematic review and meta-analysis of large animal studies. Circ Res. 2015;116(1):80-6. google scholar
  • 115. Hare JM, DiFede DL, Rieger AC, Florea V, Landin AM, El-Khorazaty J, et al. Randomized comparison of allogeneic versus autologous mesenchymal stem cells for nonischemic dilated cardiomyopathy: POSEIDON-DCM trial. J Am Coll Cardiol. 2017;69(5):526-37. google scholar
  • 116. Premer C, Blum A, Bellio MA, Schulman IH, Hurwitz BE, Parker M, et al. Allogeneic mesenchymal stem cells restore endothelial function in heart failure by stimulating endothelial progenitor cells. EBioMedicine. 2015;2(5):467-75. google scholar
  • 117. Krampera M, Cosmi L, Angeli R, Pasini A, Liotta F, Andreini A, et al. Role for interferon-gamma in the immunomodulatory activity of human bone marrow mesenchymal stem cells. Stem Cells. 2006;24(2):386-98. google scholar
  • 118. English K, Barry FP, Field-Corbett CP, Mahon BP. IFN-gamma and TNF-alpha differentially regulate immunomodulation by murine mesenchymal stem cells. Immunol Lett. 2007;110(2):91-100. google scholar
  • 119. Ryan JM, Barry F, Murphy JM, Mahon BP. Interferon-gamma does not break, but promotes the immunosuppressive capacity of adult human mesenchymal stem cells. Clin Exp Immunol. 2007;149(2):353-63. google scholar
  • 120. Ren G, Zhang L, Zhao X, et al. Mesenchymal stem cell-mediated immunosuppression occurs via concerted action of chemokines and nitric oxide. Cell Stem Cell. 2008;2(2):141-50. google scholar
  • 121. Lee RH, Pulin AA, Seo MJ, Kota DJ, Ylostalo J, Larson BL, et al. Intravenous hMSCs improve myocardial infarction in mice because cells embolized in lung are activated to secrete the anti-inflammatory protein TSG-6. Cell Stem Cell. 2009;5(1):54-63. google scholar
  • 122. Le Blanc K, Tammik C, Rosendahl K Zetterberg E, Ringden O. HLA expression and immunologic properties of differentiated and undifferentiated mesenchymal stem cells. Exp Hematol. 2003;31(10):890-6. google scholar
  • 123. Reich H, Tseliou E, de Couto G, Angert D, Valle J, Kubota Y, et al. Repeated transplantation of allogeneic cardiosphere derived cells boosts therapeutic benefits without immune sensitization in a rat model of myocardial infarction. J Heart Lung Transplant. 2016;35(11):1348-57. google scholar
  • 124. Oikonomopoulos A, Kitani T, Wu JC. Pluripotent stem cell-derived cardiomyocytes as a platform for cell therapy applications: Progress and hurdles for clinical translation. Mol Ther. 2018;26(7):1624-34. google scholar
  • 125. Ito E, Miyagawa S, Takeda M, Kawamura A, Harada A, Iseoka H, et al. Tumorigenicity assay essential for facilitating safety studies of hiPSC-derived cardiomyocytes for clinical application. Sci Rep. 2019;13;9(1):1881. google scholar
  • 126. Shiba Y, Gomibuchi T, Seto T, Wada Y, Ichimura H, Tanaka Y, et al. Allogeneic transplantation of iPS cell-derived cardiomyocytes regenerates primate hearts. Nature. 2016;20;538(7625):388-91. google scholar
  • 127. Liu YW, Chen B, Yang X, Fugate JA, Kalucki FA, Futakuchi-Tsuchida A, et al. Human embryonic stem cell-derived cardiomyocytes restore function in infarcted hearts of non-human primates. Nat Biotechnol. 2018;36(7):597-605. google scholar
  • 128. Zhao T, Zhang ZN, Rong Z, Xu Y. Immunogenicity of induced pluripotent stem cells. Nature. 2011;474(7350):212-5. google scholar
  • 129. Liu X, LiW, Fu X, Xu Y. The immunogenicity and immune tolerance of pluripotent stem cell derivatives. Front Immunol. 2017;8:645. google scholar
  • 130. Mattapally S, Pawlik KM, Fast VG, Zumaquero E, Lund FE, Randall TD, et al. Human leukocyte antigen class I and II knockout human induced pluripotent stem cell-derived cells: Jniversal donor for cell therapy. J Am Heart Assoc. 2018;7(23):e010239. google scholar
  • 131. Karre K. Natural killer cell recognition of missing self. Nat Immunol. 2008;9:477-80. google scholar
  • 132. Chidgey AP, Boyd RL. Immune privilege for stem cells: Not as simple as it looked. Cell Stem Cell. 2008;3(4):357-8. google scholar
  • 133. Nakamura Y, Miyagawa S, Yoshida S, Sasawatari S, Toyofuku T, Toda K, et al. Natural killer cells impede the engraftment of cardiomyocytes derived from induced pluripotent stem cells in syngeneic mouse model. Sci Rep. 2019;9(1):10840. google scholar
  • 134. Ayala Garcia MA, Gonzalez Yebra B, Lopez Flores AL, Guani Guerra E. The major histocompatibility complex in transplantation. J Transplant. 2012;2012:842141. google scholar
  • 135. Ingulli E. Mechanism of cellular rejection in transplantation. Pediatr Nephrol. 2010;25(1):61-74. google scholar
  • 136. Shi X, Han W, Ding J. The impact of human leukocyte antigen mismatching on graft survival and mortality in adult renal transplantation: A protocol for a systematic review and meta-analysis. Medicine (Baltimore). 2017;96(49):e8899. google scholar
  • 137. Krupnick AS, Kreisel D, Popma SH, Balsara KR, Szeto WY, Krasinskas AM, et al. Mechanism of T cell-mediated endothelial apoptosis. Transplantation. 2002;74(6):871-6. google scholar
  • 138. Metkar SS, Wang B, Aguilar-Santelises M, Raja SM, Uhlin-Hansen L, Podack E, et al. Cytotoxic cell granule-mediated apoptosis: perforin delivers granzyme B-serglycin complexes into target cells without plasma membrane pore formation. Immunity. 2002;16(3):417-28. google scholar
  • 139. Pardo J, Wallich R, Martin P, Urban C, Rongvaux A, Flavell RA, et al. Granzyme B-induced cell death exerted by ex vivo CTL: Discriminating requirements for cell death and some of its signs. Cell Death Differ. 2008;15(3):567-79. google scholar
  • 140. Horch M, Nguyen VH. Regulatory T-cell immunotherapy for allogeneic hematopoietic stem-cell transplantation. Ther Adv Hematol. 2012;3(1):29-44. google scholar
  • 141. Boros P, Bromberg JS. Human FOXP3+ regulatory T cells in transplantation. Am J Transplant. 2009;9(8):1719-24. google scholar
  • 142. Vagnozzi RJ, Maillet M, Sargent MA, Khalil H, Johansen AKZ, Schwanekamp JA, et al. An acute immune response underlies the benefit of cardiac stem cell therapy. Nature. 2020;577(7790):405-9. google scholar
  • 143. Wagner MJ, Khan M, Mohsin S. Healing the broken heart; The immunomodulatory effects of stem cell therapy. Front Immunol. 2020;11:639. google scholar
  • 144. Mohsin S, Houser SR. Cortical bone derived stem cells for cardiac wound healing. Korean Circ J. 2019;49(4):314-25. google scholar
  • 145. Urbanek K, Rota M, Cascapera S, Bearzi C, Nascimbene A, De Angelis A, et al. Cardiac stem cells possess growth factor-receptor systems that after activation regenerate the infarcted myocardium, improving ventricular function and long-term survival. Circ Res. 2005;30;97(7):663-73. google scholar
  • 146. Li TS, Cheng K, Malliaras K, Smith RR, Zhang Y, Sun B, et al. Direct comparison of different stem cell types and subpopulations reveals superior paracrine potency and myocardial repair efficacy with cardiosphere-derived cells. J Am Coll Cardiol. 2012;59(10):942-53. google scholar
  • 147. Le Blanc K, Mougiakakos D. Multipotent mesenchymal stromal cells and the innate immune system. Nat Rev Immunol. 2012;12(5):383-96. google scholar
  • 148. Cao W, Cao K, Cao J, Wang Y, Shi Y. Mesenchymal stem cells and adaptive immune responses. Immunol Lett. 2015;168(2):147-53. google scholar
  • 149. Gibon E, Lu L, Goodman SB. Aging, inflammation, stem cells, and bone healing. Stem Cell Res Ther. 2016;7:44. google scholar
  • 150. Lin L, Du L. The role of secreted factors in stem cells mediated immune regulation. Cell Immunol. 2018;326:24-32. google scholar


SHARE




Istanbul University Press aims to contribute to the dissemination of ever growing scientific knowledge through publication of high quality scientific journals and books in accordance with the international publishing standards and ethics. Istanbul University Press follows an open access, non-commercial, scholarly publishing.