Perspectives of cell therapy for myocardial infarction and heart failure based on cardiosphere cells
- Authors: Dergilev K.V.1, Vasilets I.D.1, Tsokolaeva Z.I.1,2, Zubkova E.S.1, Parfenova E.V.1,3
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Affiliations:
- National Medical Research Center for Cardiology
- Negovsky Scientific Research Institute of General Reanimatology of the Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology
- Lomonosov Moscow State University
- Issue: Vol 92, No 4 (2020)
- Pages: 111-120
- Section: Original articles
- URL: https://journals.rcsi.science/0040-3660/article/view/34117
- DOI: https://doi.org/10.26442/00403660.2020.04.000634
- ID: 34117
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Abstract
Cardiovascular diseases are the leading cause of morbidity and mortality worldwide. In recent years, researchers are attracted to the use of cell therapy based on stem cell and progenitor cells, which has been a promising strategy for cardiac repair after injury. However, conducted research using intracoronary or intramyocardial transplantation of various types of stem/progenitor cells as a cell suspension showed modest efficiency. This is due to the low degree of integration and cell survival after transplantation. To overcome these limitations, the concept of the use of multicellular spheroids modeling the natural microenvironment of cells has been proposed, which allows maintaining their viability and therapeutic properties. It is of great interest to use so-called cardial spheroids (cardiospheres) – spontaneously forming three-dimensional structures under low-adhesive conditions, consisting of a heterogeneous population of myocardial progenitor cells and extracellular matrix proteins. This review presents data on methods for creating cardiospheres, directed regulation of their properties and reparative potential, as well as the results of preclinical and clinical studies on their use for the treatment of heart diseases.
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##article.viewOnOriginalSite##About the authors
K. V. Dergilev
National Medical Research Center for Cardiology
Author for correspondence.
Email: doctorkote@gmail.com
ORCID iD: 0000-0003-2712-4997
вед. науч. сотр. лаб. ангиогенеза Института экспериментальной кардиологии
Russian Federation, MoscowIu. D. Vasilets
National Medical Research Center for Cardiology
Email: doctorkote@gmail.com
ORCID iD: 0000-0002-6367-3785
лаборант-исследователь лаб. ангиогенеза Института экспериментальной кардиологии
Russian Federation, MoscowZ. I. Tsokolaeva
National Medical Research Center for Cardiology; Negovsky Scientific Research Institute of General Reanimatology of the Federal Research and Clinical Center of Intensive Care Medicineand Rehabilitology
Email: doctorkote@gmail.com
ORCID iD: 0000-0003-2441-6062
ст. науч. сотр. лаб. ангиогенеза Института экспериментальной кардиологии
Russian Federation, MoscowE. S. Zubkova
National Medical Research Center for Cardiology
Email: doctorkote@gmail.com
ORCID iD: 0000-0002-0512-3670
мл. науч. сотр. лаб. ангиогенеза Института экспериментальной кардиологии
Russian Federation, MoscowE. V. Parfenova
National Medical Research Center for Cardiology; Lomonosov Moscow State University
Email: doctorkote@gmail.com
ORCID iD: 0000-0002-0969-5780
рук. лаб. ангиогенеза, дир. Института экспериментальной кардиологии; лаб. постгеномных технологий в медицине фак-та фундаментальной медицины
Russian Federation, MoscowReferences
- Ashur C, Frishman WH. Cardiosphere-Derived Cells and Ischemic Heart Failure. Cardiol Rev. 2018;26(1):8-21. doi: 10.1097/CRD.0000000000000173
- Barile L, Gherghiceanu M, Popescu LM, et al. Ultrastructural evidence of exosome secretion by progenitor cells in adult mouse myocardium and adult human cardiospheres. J Biomed Biotechnol. 2012;2012:354605. doi: 10.1155/2012/354605
- Bernardo BC, Ooi JY, Lin RC, McMullen JR. miRNA therapeutics: a new class of drugs with potential therapeutic applications in the heart. Future Med Chem. 2015;7(13):1771-92. doi: 10.4155/fmc.15.107
- Khodayari S, Khodayari H, Amiri AZ, et al. Inflammatory Microenvironment of Acute Myocardial Infarction Prevents Regeneration of Heart with Stem Cells Therapy. Cell Physiol Biochem. 2019;53(5):887-909. doi: 10.33594/000000180
- Menasché P. Cell therapy trials for heart regeneration – lessons learned and future directions. Nat Rev Cardiol. 2018;15(11):659-71. doi: 10.1038/s41569-018-0013-0
- Zuppinger C. 3D culture for cardiac cells. Biochim Biophys Acta. 2016;1863(7 Pt B):1873-81. doi: 10.1016/j.bbamcr.2015.11.036
- Afzal MR, Samanta A, Shah ZI, et al. Adult Bone Marrow Cell Therapy for Ischemic Heart Disease: Evidence and Insights From Randomized Controlled Trials. Circ Res. 2015;117(6):558-75. doi: 10.1161/ CIRCRESAHA.114.304792
- Gil-Perotín S, Duran-Moreno M, Cebrián-Silla A, et al. Adult neural stem cells from the subventricular zone: a review of the neurosphere assay. Anat Rec (Hoboken). 2013;296(9):1435-52. doi: 10.1002/ ar.22746
- Griffith LG, Swartz MA. Capturing complex 3D tissue physiology in vitro. Nat Rev Mol Cell Biol. 2006;7(3):211-24. doi: 10.1038/nrm1858
- Pampaloni F, Reynaud EG, Stelzer EH. The third dimension bridges the gap between cell culture and live tissue. Nat Rev Mol Cell Biol. 2007;8(10):839-45. doi: 10.1038/nrm2236
- Pedersen JA, Swartz MA. Mechanobiology in the third dimension. Ann Biomed Eng. 2005;33(11):1469-90. doi: 10.1007/s10439-005-8159-4
- Gallet R, Tseliou E, Dawkins J, et al. Intracoronary delivery of self-assembling heart-derived microtissues (cardiospheres) for prevention of adverse remodeling in a pig model of convalescent myocardial infarction. Circ Cardiovasc Interv. 2015;8(5):e002391. doi: 10.1161/ CIRCINTERVENTIONS.115.002391
- Afzal J, Chan A, Karakas MF, et al. Cardiosphere-Derived Cells Demonstrate Metabolic Flexibility That Is Influenced by Adhesion Status. JACC Basic Transl Sci. 2017;2(5):543-60. doi: 10.1016/j.jacbts. 2017.03.016
- Aghila Rani KG, Kartha CC. Effects of epidermal growth factor on proliferation and migration of cardiosphere-derived cells expanded from adult human heart. Growth Factors. 2010;28(3):157-65. doi: 10.3109/08977190903512628
- Chimenti I, Gaetani R, Forte E, et al. Serum and supplement optimization for EU GMP-compliance in cardiospheres cell culture. J Cell Mol Med. 2014;18(4):624-34. doi: 10.1111/jcmm.12210
- Messina E, De Angelis L, Frati G, et al. Isolation and expansion of adult cardiac stem cells from human and murine heart. Circ Res. 2004;95(9):911-21. doi: 10.1161/01.RES.0000147315.71699.51
- Fabrizi C, Angelini F, Chimenti I, et al. Thrombin and thrombin-derived peptides promote proliferation of cardiac progenitor cells in the form of cardiospheres without affecting their differentiation potential. J Biol Regul Homeost Agents. 2011;25(2 Suppl.):43-51.
- Chimenti I, Massai D, Morbiducci U, et al. Stem Cell Spheroids and Ex Vivo Niche Modeling: Rationalization and Scaling-Up. J Cardiovasc Transl Res. 2017;10(2):150-66. doi: 10.1007/s12265-017-9741-5
- Jochems CE, van der Valk JB, Stafleu FR, Baumans V. The use of fetal bovine serum: ethical or scientific problem? Altern Lab Anim. 2002;30(2):219-27. doi: 10.1177/026119290203000208
- Chen T, You Y, Jiang H, Wang ZZ. Epithelial-mesenchymal transition (EMT): A biological process in the development, stem cell differentiation, and tumorigenesis. J Cell Physiol. 2017;232(12):3261-72. doi: 10.1002/jcp.25797
- Forte E, Chimenti I, Rosa P, et al. EMT/MET at the Crossroad of Stemness, Regeneration and Oncogenesis: The Ying-Yang Equilibrium Recapitulated in Cell Spheroids. Cancers (Basel). 2017;9(8):98. doi: 10.3390/cancers9080098
- Forte E, Miraldi F, Chimenti I, et al. TGFβ-dependent epithelial-to-mesenchymal transition is required to generate cardiospheres from human adult heart biopsies. Stem Cells Dev. 2012;21(17):3081-90. doi: 10.1089/scd.2012.0277
- Secco I, Barile L, Torrini C, et al. Notch pathway activation enhances cardiosphere in vitro expansion. J Cell Mol Med. 2018;22(11):5583-95. doi: 10.1111/jcmm.13832
- Zakharova L, Nural-Guvener H, Gaballa MA. Cardiac explant-derived cells are regulated by Notch-modulated mesenchymal transition. PLoS One. 2012;7(5):e37800. doi: 10.1371/journal.pone.0037800
- Nemir M, Pedrazzini T. Functional role of Notch signaling in the developing and postnatal heart. J Mol Cell Cardiol. 2008;45(4):495-504. doi: 10.1016/j.yjmcc.2008.02.273
- Grieskamp T, Rudat C, Lüdtke TH, et al. Notch signaling regulates smooth muscle differentiation of epicardium-derived cells. Circ Res. 2011;108(7):813-23. doi: 10.1161/CIRCRESAHA.110.228809
- Urbanek K, Torella D, Sheikh F, et al. Myocardial regeneration by activation of multipotent cardiac stem cells in ischemic heart failure. Proc Natl Acad Sci U S A. 2005;102(24):8692-7. doi: 10.1073/pnas.0500169102
- Chimenti I, Pagano F, Cavarretta E, et al. Β-blockers treatment of cardiac surgery patients enhances isolation and improves phenotype of cardiosphere-derived cells. Sci Rep. 2016;6:36774. doi: 10.1038/srep36774
- Amirrasouli MM, Shamsara M. Comparing the in vivo and in vitro effects of hypoxia (3% O2) on directly derived cells from murine cardiac explants versus murine cardiosphere derived cells. J Stem Cells Regen Med. 2017;13(2):35-44.
- Gonzalez DM, Medici D. Signaling mechanisms of the epithelial-mesenchymal transition. Sci Signal. 2014;7(344):re8. doi: 10.1126/ scisignal.2005189
- Tan SC, Gomes RS, Yeoh KK, et al. Preconditioning of Cardiosphere-Derived Cells With Hypoxia or Prolyl-4-Hydroxylase Inhibitors Increases Stemness and Decreases Reliance on Oxidative Metabolism. Cell Transplant. 2016;25(1):35-53. doi: 10.3727/096368915X687697
- Hosoyama T, Samura M, Kudo T, et al. Cardiosphere-derived cell sheet primed with hypoxia improves left ventricular function of chronically infarcted heart. Am J Transl Res. 2015;7(12):2738-51.
- Chimenti I, Smith RR, Li TS, et al. Relative roles of direct regeneration versus paracrine effects of human cardiosphere-derived cells transplanted into infarcted mice. Circ Res. 2010;106(5):971-80. doi: 10.1161/CIRCRESAHA.109.210682
- Li TS, Cheng K, Lee ST, et al. Cardiospheres recapitulate a niche-like microenvironment rich in stemness and cell-matrix interactions, rationalizing their enhanced functional potency for myocardial repair. Stem Cells. 2010;28(11):2088-98. doi: 10.1002/stem.532
- Cho HJ, Lee HJ, Youn SW, et al. Secondary sphere formation enhances the functionality of cardiac progenitor cells. Mol Ther. 2012;20(9):1750-66. doi: 10.1038/mt.2012.109
- Redgrave RE, Tual-Chalot S, Davison BJ, et al. Cardiosphere-Derived Cells Require Endoglin for Paracrine-Mediated Angiogenesis. Stem Cell Reports. 2017;8(5):1287-98. doi: 10.1016/j.stemcr.2017.04.015
- Lee HJ, Cho HJ, Kwon YW, et al. Phenotypic modulation of human cardiospheres between stemness and paracrine activity, and implications for combined transplantation in cardiovascular regeneration. Biomaterials. 2013;34(38):9819-29. doi: 10.1016/j.biomaterials.2013.09.013
- Lee ST, White AJ, Matsushita S, et al. Intramyocardial injection of autologous cardiospheres or cardiosphere-derived cells preserves function and minimizes adverse ventricular remodeling in pigs with heart failure post-myocardial infarction. J Am Coll Cardiol. 2011;57(4):455-65. doi: 10.1016/j.jacc.2010.07.049
- Tseliou E, Kanazawa H, Dawkins J, et al. Widespread Myocardial Delivery of Heart-Derived Stem Cells by Nonocclusive Triple-Vessel Intracoronary Infusion in Porcine Ischemic Cardiomyopathy: Superior Attenuation of Adverse Remodeling Documented by Magnetic Resonance Imaging and Histology. PLoS One. 2016;11(1):e0144523. doi: 10.1371/journal.pone.0144523
- Johnston PV, Sasano T, Mills K, et al. Engraftment, differentiation, and functional benefits of autologous cardiosphere-derived cells in porcine ischemic cardiomyopathy. Circulation. 2009;120(12):1075-83. doi: 10.1161/CIRCULATIONAHA.108.816058
- Cheng K, Blusztajn A, Shen D, et al. Functional performance of human cardiosphere-derived cells delivered in an in situ polymerizable hyaluronan-gelatin hydrogel. Biomaterials. 2012;33(21):5317-24. doi: 10.1016/j.biomaterials.2012.04.006
- Tanaka Y, Hosoyama T, Mikamo A, et al. Hypoxic preconditioning of human cardiosphere-derived cell sheets enhances cellular functions via activation of the PI3K/Akt/mTOR/HIF-1α pathway. Am J Transl Res. 2017;9(2):664-73.
- Blázquez R, Sánchez-Margallo FM, Crisóstomo V, et al. Intrapericardial Delivery of Cardiosphere-Derived Cells: An Immunological Study in a Clinically Relevant Large Animal Model. PLoS One. 2016;11(2):e0149001. doi: 10.1371/journal.pone.0149001
- Gallet R, Dawkins J, Valle J, et al. Exosomes secreted by cardiosphere-derived cells reduce scarring, attenuate adverse remodelling, and improve function in acute and chronic porcine myocardial infarction. Eur Heart J. 2017;38(3):201-11. doi: 10.1093/eurheartj/ehw240
- Rogers RG, Fournier M, Sanchez L, et al. Disease-modifying bioactivity of intravenous cardiosphere-derived cells and exosomes in mdx mice. JCI Insight. 2019;4(7):e125754. doi: 10.1172/jci.insight.125754
- Lapchak PA, Boitano PD, de Couto G, Marbán E. Intravenous xenogeneic human cardiosphere-derived cell extracellular vesicles (exosomes) improves behavioral function in small-clot embolized rabbits. Experimental Neurology. 2018;307:109-17. doi: 10.1016/j.expneurol. 2018.06.007
- Tseliou E, Fouad J, Reich H, et al. Fibroblasts Rendered Antifibrotic, Antiapoptotic, and Angiogenic by Priming With Cardiosphere-Derived Extracellular Membrane Vesicles. J Am Coll Cardiol. 2015;66(6):599-611. doi: 10.1016/j.jacc.2015.05.068
- Grigorian-Shamagian L, Liu W, Fereydooni S, et al. Cardiac and systemic rejuvenation after cardiosphere-derived cell therapy in senescent rats. Eur Heart J. 2017;38(39):2957-67. doi: 10.1093/eurheartj/ehx454
- Cambier L, Giani JF, Liu W, et al. Angiotensin II-Induced End-Organ Damage in Mice Is Attenuated by Human Exosomes and by an Exosomal Y RNA Fragment. Hypertension. 2018;72(2):370-80. doi: 10.1161/HYPERTENSIONAHA.118.11239
- Ibrahim AG, Cheng K, Marbán E. Exosomes as critical agets of cardiac regeneration triggered by cell therapy. Stem Cell Reports. 2014;2(5):606-19. doi: 10.1016/j.stemcr.2014.04.006
- Malliaras K, Li TS, Luthringer D, et al. Safety and efficacy of allogeneic cell therapy in infarcted rats transplanted with mismatched cardiosphere-derived cells. Circulation. 2012;125(1):10-2. doi: 10.1161/ CIRCULATIONAHA.111.042598
- Hodgkiss-Geere HM, Argyle DJ, Corcoran BM, et al. Characterisation and cardiac directed differentiation of canine adult cardiac stem cells. Vet J. 2012;191(2):176-82. doi: 10.1016/j.tvjl.2010.12.033
- Cohn JN, Ferrari R, Sharpe N. Cardiac remodeling – concepts and clinical implications: a consensus paper from an international forum on cardiac remodeling. Behalf of an International Forum on Cardiac Remodeling. J Am Coll Cardiol. 2000;35(3):569-82. doi: 10.1016/s0735-1097(99)00630-0
- Wu QQ, Xiao Y, Yuan Y, et al. Mechanisms contributing to cardiac remodelling. Clinical Science. 2017;131(18):2319-45. doi: 10.1042/ cs20171167
- Zhang J, Wu Z, Fan Z, et al. Pericardial application as a new route for implanting stem-cell cardiospheres to treat myocardial infarction. J Physiol. 2018;596(11):2037-54. doi: 10.1113/JP275548
- Yee K, Malliaras K, Kanazawa H, et al. Allogeneic cardiospheres delivered via percutaneous transendocardial injection increase viable myocardium, decrease scar size, and attenuate cardiac dilatation in porcine ischemic cardiomyopathy. PLoS One. 2014;9(12):e113805. doi: 10.1371/journal.pone.0113805
- Tseliou E, Reich H, de Couto G, et al. Cardiospheres reverse adverse remodeling in chronic rat myocardial infarction: roles of soluble endoglin and Tgf-β signaling. Basic Res Cardiol. 2014;109(6):443. doi: 10.1007/s00395-014-0443-8
- Tseliou E, de Couto G, Terrovitis J, et al. Angiogenesis, cardiomyocyte proliferation and anti-fibrotic effects underlie structural preservation post-infarction by intramyocardially-injected cardiospheres. PLoS One. 2014;9(2):e88590. doi: 10.1371/journal.pone.0088590
- Davis DR, Zhang Y, Smith RR, et al. Validation of the cardiosphere method to culture cardiac progenitor cells from myocardial tissue. PLoS One. 2009;4(9):e7195. doi: 10.1371/journal.pone.0007195
- Kanazawa H, Tseliou E, Dawkins JF, et al. Durable Benefits of Cellular Postconditioning: Long-Term Effects of Allogeneic Cardiosphere-Derived Cells Infused After Reperfusion in Pigs with Acute Myocardial Infarction. J Am Heart Assoc. 2016;5(2):e002796. doi: 10.1161/ JAHA.115.002796
- Tseliou E, Pollan S, Malliaras K, et al. Allogeneic cardiospheres safely boost cardiac function and attenuate adverse remodeling after myocardial infarction in immunologically mismatched rat strains. J Am Coll Cardiol. 2013;61(10):1108-19. doi: 10.1016/j.jacc.2012.10.052
- Wood KJ, Issa F, Hester J. Understanding Stem Cell Immunogenicity in Therapeutic Applications. Trends Immunol. 2016;37(1):5-16. doi: 10.1016/j.it.2015.11.005
- Lauden L, Boukouaci W, Borlado LR, et al. Allogenicity of human cardiac stem/progenitor cells orchestrated by programmed death ligand 1. Circ Res. 2013;112(3):451-64. doi: 10.1161/CIRCRESAHA.112.276501
- Gallet R, de Couto G, Simsolo E, et al. Cardiosphere-derived cells reverse heart failure with preserved ejection fraction (HFpEF) in rats by decreasing fibrosis and inflammation. JACC Basic Transl Sci. 2016;1(1-2):14-28. doi: 10.1016/j.jacbts.2016.01.003
- Dutton LC, Dudhia J, Catchpole B, et al. Cardiosphere-derived cells suppress allogeneic lymphocytes by production of PGE2 acting via the EP4 receptor. Sci Rep. 2018;8(1):13351. doi: 10.1038/s41598-018-31569-1
- de Couto G, Liu W, Tseliou E, et al. Macrophages mediate cardioprotective cellular postconditioning in acute myocardial infarction. J Clin Invest. 2015;125(8):3147-62. doi: 10.1172/JCI81321
- Hasan AS, Luo L, Yan C, et al. Cardiosphere-Derived Cells Facilitate Heart Repair by Modulating M1/M2 Macrophage Polarization and Neutrophil Recruitment. PLoS One. 2016;11(10):e0165255. doi: 10.1371/journal.pone.0165255
- 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. J Cardiovasc Pharmacol Ther. 2019;24(1):70-7. doi: 10.1177/1074248418784287
- Malliaras K, Terrovitis J. Cardiomyocyte proliferation vs progenitor cells in myocardial regeneration: The debate continues. Glob Cardiol Sci Pract. 2013;2013(3):303-15. doi: 10.5339/gcsp.2013.37
- Malliaras K, Makkar RR, Smith RR, et al. Intracoronary cardiosphere-derived cells after myocardial infarction: evidence of therapeutic regeneration in the final 1-year results of the CADUCEUS trial (CArdiosphere-Derived aUtologous stem CElls to reverse ventricUlar dySfunction). J Am Coll Cardiol. 2014;63(2):110-22. doi: 10.1016/j.jacc.2013.08.724
- Maguire G, Friedman P. The Systems Biology of Stem Cell Released Molecules – Based Therapeutics. ISRN Stem Cells. 2013;1-12. doi: 10.1155/2013/784541
- Marunouchi T, Yano E, Tanonaka K. Effects of cardiosphere-derived cell transplantation on cardiac mitochondrial oxygen consumption after myocardial infarction in rats. Biomed Pharmacother. 2018;108:883-92. doi: 10.1016/j.biopha.2018.09.117
- Tang XL, Rokosh G, Sanganalmath SK, et al. Intracoronary administration of cardiac progenitor cells alleviates left ventricular dysfunction in rats with a 30-day-old infarction. Circulation. 2010;121(2):293-305. doi: 10.1161/CIRCULATIONAHA.109.871905
- Xie Y, Ibrahim A, Cheng K, et al. Importance of cell-cell contact in the therapeutic benefits of cardiosphere-derived cells. Stem Cells. 2014;32(9):2397-406. doi: 10.1002/stem.1736
- Barile L, Lionetti V, Cervio E, et al. Extracellular vesicles from human cardiac progenitor cells inhibit cardiomyocyte apoptosis and improve cardiac function after myocardial infarction. Cardiovasc Res. 2014;103(4):530-41. doi: 10.1093/cvr/cvu167
- Jafarzadeh M, Mohammad Soltani B, Ekhteraei Tousi S, Behmanesh M. Hsa-miR-497 as a new regulator in TGFβ signaling pathway and cardiac differentiation process. Gene. 2018;675:150-6. doi: 10.1016/ j.gene.2018.06.098
- Makkar RR, Smith RR, Cheng K, 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. doi: 10.1016/S0140-6736(12)60195-0
- Tarui S, Ishigami S, Ousaka D, et al. Transcoronary infusion of cardiac progenitor cells in hypoplastic left heart syndrome: Three-year follow-up of the Transcoronary Infusion of Cardiac Progenitor Cells in Patients With Single-Ventricle Physiology (TICAP) trial. J Thorac Cardiovasc Surg. 2015;150(5):1198-207,1208.e1-2. doi: 10.1016/ j.jtcvs.2015.06.076
- Chakravarty T, Makkar RR, Ascheim DD, et al. ALLogeneic Heart STem Cells to Achieve Myocardial Regeneration (ALLSTAR) Trial: Rationale and Design. Cell Transplant. 2017;26(2):205-14. doi: 10.3727/096368916X692933
- Chakravarty T, Makkar R, Henry T, et al. Multivessel intracoronary infusion of allogeneic derived cardiosphere cells in cardiomyopathy: long term outcomes of the dilated cardiomyopathy intervention with allogeneic myocardially regenerative cells (DYNAMIC STUDY). J Am Coll Cardio. 2016;68(18):B332. doi: 10.1016/j.jacc.2016.09.848
- Taylor M, Jefferies J, Byrne B, et al. Cardiac and skeletal muscle effects in the randomized HOPE-Duchenne trial. Neurology. 2019;92(8):e866-e878. doi: 10.1212/WNL.0000000000006950. PMID: 30674601.
- Dorobantu M, Popa-Fotea NM, Popa M, et al. Pursuing meaningful end-points for stem cell therapy assessment in ischemic cardiac disease. World J Stem Cells. 2017;9(12):203-18. doi: 10.4252/wjsc.v9.i12.203
- Fischer B, Meier A, Dehne A, et al. A complete workflow for the differentiation and the dissociation of hiPSC-derived cardiospheres. Stem Cell Res. 2018;32:65-72. doi: 10.1016/j.scr.2018.08.015