Cell Therapy With Human ESC-Derived Cardiac Cells: Clinical Perspectives

Adamiak, 2018, Induced pluripotent stem cell (iPSC)-Derived extracellular vesicles are safer and more effective for cardiac repair than iPSCs., Circ. Res., 122, 296, 10.1161/CIRCRESAHA.117.311769

Agarwal, 2017, Experimental, systems, and computational approaches to understanding the microrna-mediated reparative po-tential of cardiac progenitor cell–derived exosomes from pediatric pa-tientsnovelty and significance., Circ. Res., 120, 701, 10.1161/CIRCRESAHA.116.309935

Andriolo, 2018, Exosomes from human cardiac progenitor cells for therapeutic applications: development of a GMP-Grade manufacturing method., Front. Physiol., 9, 10.3389/fphys.2018.01169

Assou, 2018, Concise review: assessing the genome integrity of human induced pluripotent stem cells: what quality control metrics?, Stem Cells, 36, 814, 10.1002/stem.2797

Ban, 2017, Current strategies and challenges for purification of cardiomyocytes derived from human pluripotent stem cells., Theranostics, 7, 2067, 10.7150/thno.19427

Ban, 2014, Cell therapy with embryonic stem cell-derived cardiomyocytes encapsulated in injectable nanomatrix gel enhances cell engraftment and promotes cardiac repair., ACS Nano, 8, 10815, 10.1021/nn504617g

Bargehr, 2019, Epicardial cells derived from human embryonic stem cells augment cardiomyocyte-driven heart regeneration., Nat. Biotechnol., 37, 895, 10.1038/s41587-019-0197-9

Barile, 2018, Cardioprotection by cardiac progenitor cell-secreted exosomes: role of pregnancy-associated plasma protein-A., Cardiovasc. Res., 114, 992, 10.1093/cvr/cvy055

Bellamy, 2015, Long-term functional benefits of human embryon-ic stem cell-derived cardiac progenitors embedded into a fibrin scaffold., J. Heart Lung Transplant., 34, 1198, 10.1016/j.healun.2014.10.008

Ben-David, 2011, The tumorigenicity of human embryonic and induced pluripotent stem cells., Nat. Rev. Cancer, 11, 268, 10.1038/nrc3034

Blin, 2010, A purified population of multipotent cardiovascular progenitors derived from primate pluripotent stem cells engrafts in postmyocardial infarcted nonhuman primates., J. Clin. Invest., 120, 1125, 10.1172/JCI40120

Bobis-Wozowicz, 2015, Human induced pluripotent stem cell-derived microvesicles transmit RNAs and proteins to recipient mature heart cells modulating cell fate and behavior: hiPSC-MVs Transmit RNAs and proteins to heart cells., Stem Cells, 33, 2748, 10.1002/stem.2078

Caspi, 2007, Transplantation of human embryonic stem cell-derived cardiomyocytes improves myocardial performance in infarcted rat hearts., J. Am. Coll. Cardiol., 50, 1884, 10.1016/j.jacc.2007.07.054

Chen, 2018, Sustained release of endothelial progenitor cell-derived extracellular vesicles from shear-thinning hydrogels improves angiogene-sis and promotes function after myocardial infarction., Cardiovasc. Res., 114, 1029, 10.1093/cvr/cvy067

Chen, 2019, exosomes derived from T regulatory cells suppress CD8+ Cytotoxic T Lympho-cyte proliferation and prolong liver allograft survival., Med. Sci. Monit., 25, 4877, 10.12659/MSM.917058

Chevillet, 2014, Quantitative and stoichiometric analysis of the microRNA content of exosomes., Proc. Natl. Acad. Sci. U.S.A., 111, 14888, 10.1073/pnas.1408301111

Chong, 2014, Human embryonic-stem-cell-derived cardiomyocytes regenerate non-human primate hearts., Nature, 510, 273, 10.1038/nature13233

Citro, 2014, Comparison of human induced pluripotent stem-cell derived cardiomyocytes with human mesenchymal stem cells following acute myocardial infarction., PLoS One, 9, 10.1371/journal.pone.0116281

Ciullo, 2019, Exosomal expression of CXCR4 targets cardioprotective vesicles to myocardial infarction and improves outcome after systemic Ad-ministration., Int. J. Mol. Sci., 20, 10.3390/ijms20030468

Desgres, 2019, Clinical translation of pluripotent stem cell therapies: challenges and considerations., Cell Stem Cell, 25, 594, 10.1016/j.stem.2019.10.001

El Harane, 2018, Acellular therapeutic approach for heart failure: in vitro production of extracellular vesicles from human cardiovascular progeni-tors., Eur. Heart J., 39, 1835, 10.1093/eurheartj/ehy012

Erdö, 2003, Host-dependent tumorigenesis of embryonic stem cell transplantation in experimental stroke., J. Cereb. Blood Flow Metab., 23, 780, 10.1097/01.WCB.0000071886.63724.FB

Fernandes, 2015, Comparison of human embryonic stem cell-derived car-diomyocytes, cardiovascular progenitors, and bone marrow mononu-clear cells for cardiac repair., Stem Cell Rep., 5, 753, 10.1016/j.stemcr.2015.09.011

Florea, 2017, Dose comparison study of allogeneic mesenchymal stem cells in patients with ischemic cardiomyopathy (The TRIDENT Study)., Circ. Res., 121, 1279, 10.1161/CIRCRESAHA.117.311827

Gallet, 2017, Exosomes secreted by cardiosphere-derived cells reduce scarring, attenuate adverse remodelling, and improve function in acute and chronic porcine myocardial infarction., Eur. Heart J., 38, 201, 10.1093/eurheartj/ehw240

Gao, 2018, Large cardiac muscle patches engineered from human induced-pluripotent stem cell–derived cardiac cells improve recovery from myocardial infarction in swine., Circulation, 137, 1712, 10.1161/CIRCULATIONAHA.117.030785

Garbern, 2013, Cardiac stem cell therapy and the promise of heart regeneration., Cell Stem Cell, 12, 689, 10.1016/j.stem.2013.05.008

Garikipati, 2018, Ex-tracellular vesicles and the application of system biology and computational modeling in cardiac repair., Circ. Res., 123, 188, 10.1161/CIRCRESAHA.117.311215

Goldring, 2011, Assessing the safety of stem cell therapeutics., Cell Stem Cell, 8, 618, 10.1016/j.stem.2011.05.012

Guan, 2020, Transplantation of human induced pluripotent stem cell-derived cardiomyo-cytes improves myocardial function and reverses ventricular remodeling in infarcted rat hearts., Stem Cell Res. Ther., 11, 10.1186/s13287-020-01602-0

Guo, 2020, Stem cell-derived cell sheet transplantation for heart tissue repair in myocardial infarction., Stem Cell Res. Ther., 11, 10.1186/s13287-019-1536-y

Halbach, 2014, Cell persistence and electrical integration of transplanted fetal cardiomyocytes from different developmental stages., Int. J. Cardiol., 171, e122, 10.1016/j.ijcard.2013.12.115

Han, 2019, Human umbilical cord mesenchymal stem cell derived exosomes encapsulated in functional peptide hydrogels promote cardiac repair., Biomater. Sci., 7, 2920, 10.1039/C9BM00101H

Huang, 2020, An off-the-shelf artificial cardiac patch improves cardiac repair after myocardial infarction in rats and pigs., Sci. Transl. Med., 12, 10.1126/scitranslmed.aat9683

Huang, 2010, Embryonic stem cell-derived endothelial cells engraft into the is-chemic hindlimb and restore perfusion., Arterioscler. Thromb. Vasc. Biol., 30, 984, 10.1161/ATVBAHA.110.202796

Hung, 2015, Stabilization of Exosome-targeting Peptides via Engineered Glycosylation., J. Biol. Chem., 290, 8166, 10.1074/jbc.M114.621383

Ichimura, 2020, Increased predominance of the matured ventricular subtype in embryonic stem cell-derived cardiomyocytes in vivo., Sci. Rep., 10, 10.1038/s41598-020-68373-9

Iseoka, 2018, Pivotal role of non-cardiomyocytes in electromechanical and therapeutic potential of induced pluripotent stem cell-derived engi-neered cardiac tissue., Tissue Eng Part A, 24, 287, 10.1089/ten.TEA.2016.0535

Ishida, 2019, Transplantation of human-induced pluripotent stem cell-derived cardiomyocytes is superior to somatic stem cell therapy for restoring cardiac function and oxygen consumption in a porcine model of myocardial infarction., Transplantation, 103, 291, 10.1097/TP.0000000000002384

Kabat, 2020, Trends in mesenchy-mal stem cell clinical trials 2004-2018: Is efficacy optimal in a narrow dose range?, Stem Cells Transl. Med., 9, 17, 10.1002/sctm.19-0202

Kervadec, 2016, Cardiovascular progenitor–derived extracellular vesicles recapitulate the beneficial effects of their parent cells in the treatment of chronic heart failure., J. Heart Lung Trans Plantation, 35, 795, 10.1016/j.healun.2016.01.013

Khan, 2015, Embryonic stem cell-derived exosomes promote en-dogenous repair mechanisms and enhance cardiac function following myocardial infarction., Circ. Res., 117, 52, 10.1161/CIRCRESAHA.117.305990

Kobold, 2020, A manually curated database on clinical studies in-volving cell products derived from human pluripotent stem cells., Stem Cell Rep., 15, 546, 10.1016/j.stemcr.2020.06.014

Könemann, 2019, Cardioprotective effect of the secretome of Sca-1+ and Sca-1- cells in heart failure: not equal, but equally important?, Cardiovas. Res.., 116, 566, 10.1093/cvr/cvz140

Le, 2019, Expansion culture of human pluripotent stem cells and production of cardiomyocytes., Bioengineering, 6, 10.3390/bioengineering6020048

Lee, 2017, Comparison of non-coding RNAs in exosomes and functional efficacy of human embryonic stem cell- versus induced pluripotent stem cell-derived cardiomyocytes., Stem Cells, 35, 2138, 10.1002/stem.2669

Li, 2012, 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., 59, 942, 10.1016/j.jacc.2011.11.029

Liao, 2019, Potent im-munomodulation and angiogenic effects of mesenchymal stem cells versus cardiomyocytes derived from pluripotent stem cells for treatment of heart failure., Stem Cell Res. Ther., 10, 10.1186/s13287-019-1183-3

Lima Correa, 2020, Extracellular vesicles from human cardiovascular pro-genitors trigger a reparative immune response in infarcted hearts., Cardi Ovasc. Res., 12, 10.1093/cvr/cvaa028

Liu, 2018, Cardiac recovery via extended cell-free delivery of extracellular vesicles secreted by cardiomyocytes derived from induced pluripotent stem cells., Nat. Biomed. Eng., 2, 293, 10.1038/s41551-018-0229-7

Liu, 2018, Human embryonic stem cell-derived cardiomyocytes restore function in infarcted hearts of non-human primates., Nat. Biotechnol., 36, 597, 10.1038/nbt.4162

Lo, 2016, Cell surface glycoengineering improves selectin-mediated ad-hesion of mesenchymal stem cells (MSCs) and cardiosphere-derived cells (CDCs): pilot validation in porcine ischemia-reperfusion model., Bio Mater., 74, 19, 10.1016/j.biomaterials.2015.09.026

Luo, 2014, Targeting survival pathways to create infarct-spanning bridges of human embryonic stem cell-derived cardiomyocytes., J. Thorac. Car Diovasc. Surg., 148, 3180.e1, 10.1016/j.jtcvs.2014.06.087

Malik, 2013, Cardiac myocyte exosomes: stability, HSP60, and proteomics., Am. J. Physiol. Heart Circ. Physiol., 304, H954, 10.1152/ajpheart.00835.2012

Menasché, 2015, Towards a clinical use of human embryonic stem cell-derived cardiac progenitors: a translational experience., Eur. Heart J., 36, 743, 10.1093/eurheartj/ehu192

Menasché, 2018, Transplantation of human embryonic stem cell-derived cardiovascular progenitors for severe ischemic left ventricular dys-function., J. Am. Coll. Cardiol., 71, 429, 10.1016/j.jacc.2017.11.047

Milano, 2019, Intravenous administration of cardiac progenitor cell-derived exosomes protects against doxorubicin/trastuzumab-induced cardiac toxicity., Cardiovasc. Res., 116, 383, 10.1093/cvr/cvz108

Mohsin, 2011, Empowering adult stem cells for myocardial regeneration., Circ. Res., 109, 1415, 10.1161/CIRCRESAHA.111.243071

Moon, 2017, From bench to market: preparing human pluripotent stem cells derived cardiomyocytes for various applications., Int. J. Stem Cells, 10, 1, 10.15283/ijsc17024

Morishita, 2017, Pharmacokinetics of exosomes-an important factor for elucidating the biologi-cal roles of exosomes and for the development of exosome-based therapeutics., J. Pharm. Sci., 106, 2265, 10.1016/j.xphs.2017.02.030

Neofytou, 2015, Hurdles to clinical translation of human induced pluripotent stem cells., J. Clin. In Vest, 125, 2551, 10.1172/JCI80575

Nizzardo, 2014, Minimally invasive transplantation of iPSC-derived ALDHhiSS-CloVLA4+ neural stem cells effectively improves the phenotype of an amyotrophic lateral sclerosis model., Hum. Mol. Genet., 23, 342, 10.1093/hmg/ddt425

Okano, 2019, Therapeutic potential of pluripotent stem cells for cardiac repair after myocardial infarction., Biol. Pharma Ceut. Bull., 42, 524, 10.1248/bpb.b18-00257

Oliveira, 2014, Concise review: ge-nomic instability in human stem cells: current status and future challeng-es., Stem Cells, 32, 2824, 10.1002/stem.1796

Patil, 2019, The art of intercellular wireless communications: exosomes in heart disease and therapy., Front. Cell Dev. Biol., 7, 10.3389/fcell.2019.00315

Perin, 2015, A Phase II dose-escalation study of allogeneic mesenchymal precursor cells in patients with ischemic or nonischemic heart failurenovelty and significance., Circ. Res., 117, 576, 10.1161/CIRCRESAHA.115.306332

Priest, 2015, Preclinical safety of human embryonic stem cell-derived oligodendrocyte progenitors supporting clinical trials in spinal cord injury., Regen. Med., 10, 939, 10.2217/rme.15.57

Ratajczak, 2006, Embryonic stem cell-derived microvesicles reprogram hematopoietic progenitors: evidence for horizontal transfer of mRNA and protein deliv-ery., Leukemia, 20, 847, 10.1038/sj.leu.2404132

Riegler, 2015, Human engineered heart muscles engraft and survive long term in a rodent myocardial infarction model., Circ. Res., 117, 720, 10.1161/CIRCRESAHA.115.306985

Rogers, 2019, Disease-modifying bioactivity of intravenous cardiosphere-derived cells and exosomes in mdx mice., JCI Insight, 4, 10.1172/jci.insight.125754

Romagnuolo, 2019, Human embryonic stem cell-derived cardiomy-ocytes regenerate the infarcted pig heart but induce ventricular tach-yarrhythmias., Stem Cell Rep., 12, 967, 10.1016/j.stemcr.2019.04.005

Sackstein, 2009, Glycosyltransferase-programmed stereosubstitution (GPS) to create HCELL: engineering a roadmap for cell migration., Immunol. Rev., 230, 51, 10.1111/j.1600-065X.2009.00792.x

Sadek, 2020, Toward the goal of human heart regenera-tion., Cell Stem Cell, 26, 7, 10.1016/j.stem.2019.12.004

Santoso, 2020, Exosomes from induced pluripotent stem cell–derived cardio-myocytes promote autophagy for myocardial repair., J. Am. Heart Assoc., 9, 10.1161/JAHA.119.014345

Sato, 2019, Tumorigenicity assessment of cell therapy products: the need for global consensus and points to consider., Cytotherapy, 21, 1095, 10.1016/j.jcyt.2019.10.001

Schwach, 2020, Expandable human cardiovascular progenitors from stem cells for regenerating mouse heart after myocardial infarction., Cardiovasc. Res., 116, 545, 10.1093/cvr/cvz181

Shao, 2017, MiRNA-sequence indicates that mesenchymal stem cells and exosomes have similar mechanism to enhance cardiac repair., BioMed Res. Int., 2017, 1, 10.1155/2017/4150705

Sharma, 2017, A deep proteome analysis identifies the complete secretome as the functional unit of human cardiac progenitor cells., Circ. Res., 120, 816, 10.1161/CIRCRESAHA.116.309782

Shiba, 2016, Allogeneic transplantation of iPS cell-derived cardiomyocytes regenerates primate hearts., Nature, 538, 388, 10.1038/nature19815

Singla, 2012, Embryonic stem cells improve cardiac function in doxorubicin-induced cardiomyopathy mediated through multiple mechanisms., Cell Transplant, 21, 1919, 10.3727/096368911X627552

Smith, 2007, Regenerative potential of cardiosphere-derived cells expanded from percutaneous endomyocardial biopsy specimens., Circulation, 115, 896, 10.1161/CIRCULATIONAHA.106.655209

Sun, 2018, Intravenous mesenchymal stem cell-derived exosomes ameliorate myocardial inflammation in the dilated cardiomyopathy., Biochem. Biophys. Res. Commun., 503, 2611, 10.1016/j.bbrc.2018.08.012

Tang, 2011, An antibody against SSEA-5 glycan on human pluripotent stem cells enables removal of teratoma-forming cells., Nat. Biotechnol., 29, 829, 10.1038/nbt.1947

Tang, 2018, Repeated administrations of cardiac progenitor cells are superior to a single administration of an equivalent cumulative dose., J Am Heart Assoc., 7, 10.1161/JAHA.117.007400

Taylor, 2019, Cardiac and skeletal muscle effects in the randomized HOPE-Duchenne trial., Neurology, 92, e866, 10.1212/WNL.0000000000006950

Théry, 2018, Minimal information for studies of extra-cellular vesicles 2018 (MISEV2018): a position statement of the Interna-tional society for extracellular vesicles and update of the MISEV2014 guidelines., J. Extracell. Vesicles, 7, 10.1080/20013078.2018.1535750

Tiburcy, 2017, Defined engineered human myocardium with advanced maturation for applications in heart failure modeling and repair., Cir Culation, 135, 1832, 10.1161/CIRCULATIONAHA.116.024145

Timmers, 2011, Human mesenchymal stem cell-conditioned medium improves cardiac function following myocardial infarction., Stem Cell Res., 6, 206, 10.1016/j.scr.2011.01.001

van Berlo, 2014, c-kit+ cells minimally contribute cardiomyocytes to the heart., Nature, 509, 337, 10.1038/nature13309

van Laake, 2009, Improvement of mouse cardiac function by hESC-derived cardiomyocytes correlates with vascularity but not graft size., Stem Cell Res., 3, 106, 10.1016/j.scr.2009.05.004

van Laake, 2007, Human embryonic stem cell-derived cardiomy-ocytes survive and mature in the mouse heart and transiently improve function after myocardial infarction., Stem Cell Res, 1, 9, 10.1016/j.scr.2007.06.001

Vandergriff, 2018, Targeting regenerative exosomes to myocardial infarction us-ing cardiac homing peptide., Theranostics, 8, 1869, 10.7150/thno.20524

Vandergriff, 2015, Intravenous cardiac stem cell-derived exosomes ameliorate cardiac dysfunction in doxorubicin induced dilated cardiomyopathy., Stem Cells Int., 2015, 1, 10.1155/2015/960926

Walker, 2012, Bone marrow–derived stromal cell therapy for traumatic brain injury is neuroprotective via stimulation of non-neurologic organ sys-tems., Surgery, 152, 790, 10.1016/j.surg.2012.06.006

Waters, 2018, Stem cell-inspired secretome-rich injectable hydrogel to repair injured cardiac tissue., Acta Biomater., 69, 95, 10.1016/j.actbio.2017.12.025

Whyte, 2018, Sustained release of targeted cardiac therapy with a replenishable implanted epicardial reservoir., Nat. Biomed. Eng., 2, 416, 10.1038/s41551-018-0247-5

Wiklander, 2019, Advances in therapeutic applications of extracellular vesicles., Sci. Transl. Med., 11, 10.1126/scitranslmed.aav8521

Wiklander, 2015, Extracellular vesicle in vivo biodistribution is de-termined by cell source, route of administration and targeting., J. Extracell Vesicles, 4, 10.3402/jev.v4.26316

Wysoczynski, 2020, A realistic appraisal of the use of embryonic stem cell-based therapies for cardiac repair., Eur. Heart J., 41, 2397, 10.1093/eurheartj/ehz787

Xu, 2019, Targeted Disruption of HLA Genes via CRISPR-Cas9 Generates iPSCs with Enhanced Immune Compatibility., Cell Stem Cell, 24, 566.e1, 10.1016/j.stem.2019.02.005

Xu, 2019, Exosomes derived from pro-inflammatory bone marrow-derived mesenchymal stem cells reduce inflammation and myocardial injury via mediating macrophage polarization., J. Cell. Mol. Med., 23, 7617, 10.1111/jcmm.14635

Yarbrough, 2003, Large animal models of congestive heart failure: a critical step in translating basic observations into clinical applications., J. Nucl. Cardiol., 10, 77, 10.1067/mnc.2003.16

Ye, 2015, Treatment with hESC-derived myocardial precursors improves cardiac function after a myocardial infarction., PLoS One, 10, 10.1371/journal.pone.0131123

Yee, 2014, Allogeneic cardiospheres delivered via percutaneous transen-docardial injection increase viable myocardium, decrease scar size, and attenuate cardiac dilatation in porcine ischemic cardiomyopathy., PLoS One, 9, 10.1371/journal.pone.0113805

Yin, 2019, Manufacturing of primed mesenchymal stromal cells for therapy., Nat. Biomed. Eng., 3, 90, 10.1038/s41551-018-0325-8

Yoshida, 2020, Syngeneic mesenchymal stem cells reduce im-mune rejection after induced pluripotent stem cell-derived allogeneic cardiomyocyte transplantation., Sci. Rep., 10, 10.1038/s41598-020-58126-z

Yuan, 2009, Transfer of microRNAs by embryonic stem cell mi-crovesicles., PLoS One, 4, 10.1371/journal.pone.0004722

Yuan, 2019, Exosomes derived from human primed mesenchymal stem cells induce mitosis and potentiate growth factor secretion., Stem Cells Dev., 28, 398, 10.1089/scd.2018.0200

Zhao, 2019, Mesenchymal stromal cell-derived exosomes attenuate myocardial ischaemia-reperfusion injury through miR-182-regulated macrophage polarization., Cardiovasc. Res., 115, 1205, 10.1093/cvr/cvz040

Zhu, 2018, Lack of Re-muscularization following transplantation of human embryonic stem cell-derived cardiovascular progenitor cells in infarcted nonhuman primates., Circ. Res., 122, 958, 10.1161/CIRCRESAHA.117.311578