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2000
Volume 21, Issue 5
  • ISSN: 1573-403X
  • E-ISSN: 1875-6557
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Abstract

Chronic ischemic heart failure (CIHF), caused by myocardial injury and cell loss, is a growing public health concern. Despite substantial investments in pharmaco- and device therapies for acute myocardial infarction and CIHF over the past decades, long-term prognosis has shown little improvement. There is a clear need to develop novel therapeutic strategies capable of attenuating progression from acute to chronic myocardial damage, reducing adverse myocardial remodeling, and enhancing myocardial contractility. Cell-based approaches are an important direction in basic and clinical research. Nevertheless, candidate cell types tested to-date in experimental and human studies show several fundamental limitations, including insufficient quantities and potency, poor myocardial uptake, immunogenicity and/or risk of tumorigenicity. Human umbilical cord matrix is a rich source of mesenchymal stem cells (Wharton’s jelly mesenchymal stem cells, WJMSCs). WJMSCs are naturally low-immunogenic, demonstrate high plasticity and proliferation capacity, and exhibit an absence of tumorigenic potential. Moreover, by producing specific anti-inflammatory cytokines and chemokines, they reduce the inflammatory response (hence their use in graft--host disease) and have pro-angiogenic, anti-apoptotic, and anti-fibrotic properties, making them a natural player in myocardial repair and regeneration. Furthermore, WJMSCs can be expanded with high genomic stability and full clonogenic potential and can be standardized as an “off-the-shelf” next-generation advanced therapy medicinal product (ATMP). This review aggregates essential, contemporary information on the properties and fundamental mechanisms of WJMSCs addressing the process of infarct healing and chronic myocardial injury. It discusses outcomes from pre-clinical studies, demonstrating improvements in myocardial function and reductions in fibrosis in animal models, paving the way for human ATMP trials.

© 2025 The Author(s). Published by Bentham Science Publishers. 
This is an open access article published under CC BY 4.0 https://creativecommons.org/licenses/by/4.0/legalcode
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References

  1. PearsonJ. SipidoK.R. MusialekP. van GilstW.H. The cardiovascular research community calls for action to address the growing burden of cardiovascular disease.Cardiovasc. Res.201911510e96e9810.1093/cvr/cvz17531334808
     [Google Scholar]
  2. BloemkolkD DimopoulouC ForbesD Strategic research agenda for cardiovascular diseases (SRA CVD). Challenges and opportunities for cardiovascular disease researchAvailable from: https://www.era-cvd.eu/396.php 2019
  3. StoneG.W. SelkerH.P. ThieleH. PatelM.R. UdelsonJ.E. OhmanE.M. MaeharaA. EitelI. GrangerC.B. JenkinsP.L. NicholsM. Ben-YehudaO. Relationship between infarct size and outcomes following primary PCI.J. Am. Coll. Cardiol.201667141674168310.1016/j.jacc.2016.01.06927056772
     [Google Scholar]
  4. KeeleyE.C. BouraJ.A. GrinesC.L. Primary angioplasty versus intravenous thrombolytic therapy for acute myocardial infarction: A quantitative review of 23 randomised trials.Lancet20033619351132010.1016/S0140‑6736(03)12113‑712517460
     [Google Scholar]
  5. DalbyM. BouzamondoA. LechatP. MontalescotG. Transfer for primary angioplasty versus immediate thrombolysis in acute myocardial infarction: A meta-analysis.Circulation2003108151809181410.1161/01.CIR.0000091088.63921.8C14530206
     [Google Scholar]
  6. ISIS-2 (Second International Study of Infarct Survival) Collaborative Group Randomised trial of intravenous streptokinase, oral aspirin, both, or neither among 17,187 cases of suspected acute myocardial infarction: ISIS-2. ISIS-2 (Second International Study of Infarct Survival) Collaborative Group.Lancet1988286073493602899772
     [Google Scholar]
  7. FusterV. DykenM.L. VokonasP.S. HennekensC. Special Writing Group Aspirin as a therapeutic agent in cardiovascular disease.Circulation199387265967510.1161/01.CIR.87.2.6598425313
     [Google Scholar]
  8. MehtaS.R. YusufS. PetersR.J.G. BertrandM.E. LewisB.S. NatarajanM.K. MalmbergK. RupprechtH.J. ZhaoF. ChrolaviciusS. CoplandI. FoxK.A.A. Clopidogrel in Unstable angina to prevent Recurrent Events trial (CURE) Investigators Effects of pretreatment with clopidogrel and aspirin followed by long-term therapy in patients undergoing percutaneous coronary intervention: The PCI-CURE study.Lancet2001358928152753310.1016/S0140‑6736(01)05701‑411520521
     [Google Scholar]
  9. VerdoiaM. SchafferA. BarbieriL. CassettiE. PiccoloR. GalassoG. MarinoP. SinigagliaF. De LucaG. Benefits from new ADP antagonists as compared with clopidogrel in patients with stable angina or acute coronary syndrome undergoing invasive management: A meta-analysis of randomized trials.J. Cardiovasc. Pharmacol.201463433935010.1097/FJC.000000000000005224336016
     [Google Scholar]
  10. SchwartzG.G. OlssonA.G. EzekowitzM.D. GanzP. OliverM.F. WatersD. ZeiherA. ChaitmanB.R. LeslieS. SternT. Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) Study Investigators Effects of atorvastatin on early recurrent ischemic events in acute coronary syndromes: The MIRACL study: A randomized controlled trial.JAMA2001285131711171810.1001/jama.285.13.171111277825
     [Google Scholar]
  11. AfilaloJ. MajdanA.A. EisenbergM.J. Intensive statin therapy in acute coronary syndromes and stable coronary heart disease: A comparative meta-analysis of randomised controlled trials.Heart200793891492110.1136/hrt.2006.11250817277349
     [Google Scholar]
  12. NavareseE.P. KowalewskiM. AndreottiF. van WelyM. CamaroC. KolodziejczakM. GornyB. WiriantaJ. KubicaJ. KelmM. de BoerM.J. SuryapranataH. Meta-analysis of time-related benefits of statin therapy in patients with acute coronary syndrome undergoing percutaneous coronary intervention.Am. J. Cardiol.2014113101753176410.1016/j.amjcard.2014.02.03424792742
     [Google Scholar]
  13. PanY. TanY. LiB. LiX. Efficacy of high-dose rosuvastatin preloading in patients undergoing percutaneous coronary intervention: A meta-analysis of fourteen randomized controlled trials.Lipids Health Dis.20151419710.1186/s12944‑015‑0095‑126306625
     [Google Scholar]
  14. DargieH.J. Effect of carvedilol on outcome after myocardial infarction in patients with left-ventricular dysfunction: The CAPRICORN randomised trial.Lancet200135792661385139010.1016/S0140‑6736(00)04560‑811356434
     [Google Scholar]
  15. JooS.J. KimS.Y. ChoiJ.H. ParkH.K. BeomJ.W. LeeJ.G. ChaeS.C. KimH.S. KimY.J. ChoM.C. KimC.J. RhaS.W. YoonJ. JeongM.H. Effect of beta-blocker therapy in patients with or without left ventricular systolic dysfunction after acute myocardial infarction.Eur. Heart J. Cardiovasc. Pharmacother.20217647548210.1093/ehjcvp/pvaa02932289158
     [Google Scholar]
  16. PfefferM.A. BraunwaldE. MoyéL.A. BastaL. BrownE.J.Jr CuddyT.E. DavisB.R. GeltmanE.M. GoldmanS. FlakerG.C. KleinM. LamasG.A. PackerM. RouleauJ. RouleauJ.L. RutherfordJ. WertheimerJ.H. HawkinsC.M. The SAVE Investigators Effect of captopril on mortality and morbidity in patients with left ventricular dysfunction after myocardial infarction. Results of the survival and ventricular enlargement trial.N. Engl. J. Med.19923271066967710.1056/NEJM1992090332710011386652
     [Google Scholar]
  17. The Acute Infarction Ramipril Efficacy (AIRE) Study Investigators Effect of ramipril on mortality and morbidity of survivors of acute myocardial infarction with clinical evidence of heart failure.Lancet199334288758218288104270
     [Google Scholar]
  18. KøberL. Torp-PedersenC. CarlsenJ.E. BaggerH. EliasenP. LyngborgK. VidebækJ. ColeD.S. AuclertL. PaulyN.C. AliotE. PerssonS. CammA.J. Trandolapril Cardiac Evaluation (TRACE) Study Group A clinical trial of the angiotensin-converting-enzyme inhibitor trandolapril in patients with left ventricular dysfunction after myocardial infarction.N. Engl. J. Med.1995333251670167610.1056/NEJM1995122133325037477219
     [Google Scholar]
  19. SleightP. Angiotensin II and trials of cardiovascular outcomes11Reprints are not available.Am. J. Cardiol.2002892111610.1016/S0002‑9149(01)02322‑011835905
     [Google Scholar]
  20. MossA.J. ZarebaW. HallW.J. KleinH. WilberD.J. CannomD.S. DaubertJ.P. HigginsS.L. BrownM.W. AndrewsM.L. Multicenter Automatic Defibrillator Implantation Trial II Investigators Prophylactic implantation of a defibrillator in patients with myocardial infarction and reduced ejection fraction.N. Engl. J. Med.20023461287788310.1056/NEJMoa01347411907286
     [Google Scholar]
  21. The CONSENSUS Trial Study Group Enalapril for congestive heart failure.N. Engl. J. Med.1987317211349135110.1056/NEJM1987111931721122825013
     [Google Scholar]
  22. YusufS. PittB. DavisC.E. HoodW.B. CohnJ.N. SOLVD Investigators Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure.N. Engl. J. Med.1991325529330210.1056/NEJM1991080132505012057034
     [Google Scholar]
  23. MERIT-HF Study Group Effect of metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL randomised intervention trial in-congestive heart failure (MERIT-HF).Lancet199935391692001200710.1016/S0140‑6736(99)04440‑210376614
     [Google Scholar]
  24. PackerM. BristowM.R. CohnJ.N. ColucciW.S. FowlerM.B. GilbertE.M. ShustermanN.H. U.S. Carvedilol Heart Failure Study Group The effect of carvedilol on morbidity and mortality in patients with chronic heart failure.N. Engl. J. Med.1996334211349135510.1056/NEJM1996052333421018614419
     [Google Scholar]
  25. PackerM. FowlerM.B. RoeckerE.B. CoatsA.J.S. KatusH.A. KrumH. MohacsiP. RouleauJ.L. TenderaM. StaigerC. HolcslawT.L. Amann-ZalanI. DeMetsD.L. Carvedilol Prospective Randomized Cumulative Survival (COPERNICUS) Study Group Effect of carvedilol on the morbidity of patients with severe chronic heart failure: Results of the carvedilol prospective randomized cumulative survival (COPERNICUS) study.Circulation2002106172194219910.1161/01.CIR.0000035653.72855.BF12390947
     [Google Scholar]
  26. FlatherM.D. ShibataM.C. CoatsA.J.S. Van VeldhuisenD.J. ParkhomenkoA. BorbolaJ. Cohen-SolalA. DumitrascuD. FerrariR. LechatP. Soler-SolerJ. TavazziL. SpinarovaL. TomanJ. BöhmM. AnkerS.D. ThompsonS.G. Poole-WilsonP.A. SENIORS Investigators Randomized trial to determine the effect of nebivolol on mortality and cardiovascular hospital admission in elderly patients with heart failure (SENIORS).Eur. Heart J.200526321522510.1093/eurheartj/ehi11515642700
     [Google Scholar]
  27. CIBIS-II Investigators and Committees The cardiac insufficiency bisoprolol study II (CIBIS-II): A randomised trial.Lancet1999353914691310.1016/S0140‑6736(98)11181‑910023943
     [Google Scholar]
  28. ClelandJ.G.F. BuntingK.V. FlatherM.D. AltmanD.G. HolmesJ. CoatsA.J.S. ManzanoL. McMurrayJ.J.V. RuschitzkaF. van VeldhuisenD.J. von LuederT.G. BöhmM. AnderssonB. KjekshusJ. PackerM. RigbyA.S. RosanoG. WedelH. HjalmarsonÅ. WikstrandJ. KotechaD. Beta-blockers in Heart Failure Collaborative Group Beta-blockers for heart failure with reduced, mid-range, and preserved ejection fraction: An individual patient-level analysis of double-blind randomized trials.Eur. Heart J.2018391263510.1093/eurheartj/ehx56429040525
     [Google Scholar]
  29. PittB. ZannadF. RemmeW.J. CodyR. CastaigneA. PerezA. PalenskyJ. WittesJ. Randomized Aldactone Evaluation Study Investigators The effect of spironolactone on morbidity and mortality in patients with severe heart failure.N. Engl. J. Med.19993411070971710.1056/NEJM19990902341100110471456
     [Google Scholar]
  30. ZannadF. McMurrayJ.J.V. KrumH. van VeldhuisenD.J. SwedbergK. ShiH. VincentJ. PocockS.J. PittB. EMPHASIS-HF Study Group Eplerenone in patients with systolic heart failure and mild symptoms.N. Engl. J. Med.20113641112110.1056/NEJMoa100949221073363
     [Google Scholar]
  31. McMurrayJ.J.V. SolomonS.D. InzucchiS.E. KøberL. KosiborodM.N. MartinezF.A. PonikowskiP. SabatineM.S. AnandI.S. BělohlávekJ. BöhmM. ChiangC.E. ChopraV.K. de BoerR.A. DesaiA.S. DiezM. DrozdzJ. DukátA. GeJ. HowlettJ.G. KatovaT. KitakazeM. LjungmanC.E.A. MerkelyB. NicolauJ.C. O’MearaE. PetrieM.C. VinhP.N. SchouM. TereshchenkoS. VermaS. HeldC. DeMetsD.L. DochertyK.F. JhundP.S. BengtssonO. SjöstrandM. LangkildeA.M. DAPA-HF Trial Committees and Investigators Dapagliflozin in patients with heart failure and reduced ejection fraction.N. Engl. J. Med.2019381211995200810.1056/NEJMoa191130331535829
     [Google Scholar]
  32. PackerM. AnkerS.D. ButlerJ. FilippatosG. PocockS.J. CarsonP. JanuzziJ. VermaS. TsutsuiH. BrueckmannM. JamalW. KimuraK. SchneeJ. ZellerC. CottonD. BocchiE. BöhmM. ChoiD.J. ChopraV. ChuquiureE. GiannettiN. JanssensS. ZhangJ. Gonzalez JuanateyJ.R. KaulS. Brunner-La RoccaH.P. MerkelyB. NichollsS.J. PerroneS. PinaI. PonikowskiP. SattarN. SenniM. SerondeM.F. SpinarJ. SquireI. TaddeiS. WannerC. ZannadF. EMPEROR-Reduced Trial Investigators Cardiovascular and renal outcomes with empagliflozin in heart failure.N. Engl. J. Med.2020383151413142410.1056/NEJMoa202219032865377
     [Google Scholar]
  33. McMurrayJ.J.V. PackerM. DesaiA.S. GongJ. LefkowitzM.P. RizkalaA.R. RouleauJ.L. ShiV.C. SolomonS.D. SwedbergK. ZileM.R. PARADIGM-HF Investigators and Committees Angiotensin-neprilysin inhibition versus enalapril in heart failure.N. Engl. J. Med.201437111993100410.1056/NEJMoa140907725176015
     [Google Scholar]
  34. ZhouX. ZhuH. ZhengY. TanX. TongX. A systematic review and meta-analysis of sacubitril-valsartan in the treatment of ventricular remodeling in patients with heart failure after acute myocardial infarction.Front. Cardiovasc. Med.2022995394810.3389/fcvm.2022.95394836304540
     [Google Scholar]
  35. FarisR. FlatherM. PurcellH. HeneinM. Poole-WilsonP. CoatsA. Current evidence supporting the role of diuretics in heart failure: A meta analysis of randomised controlled trials.Int. J. Cardiol.200282214915810.1016/S0167‑5273(01)00600‑311853901
     [Google Scholar]
  36. GrangerC.B. McMurrayJ.J.V. YusufS. HeldP. MichelsonE.L. OlofssonB. ÖstergrenJ. PfefferM.A. SwedbergK. CHARM Investigators and Committees Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function intolerant to angiotensin-converting-enzyme inhibitors: The CHARM-Alternative trial.Lancet2003362938677277610.1016/S0140‑6736(03)14284‑513678870
     [Google Scholar]
  37. BardyG.H. LeeK.L. MarkD.B. PooleJ.E. PackerD.L. BoineauR. DomanskiM. TroutmanC. AndersonJ. JohnsonG. McNultyS.E. Clapp-ChanningN. Davidson-RayL.D. FrauloE.S. FishbeinD.P. LuceriR.M. IpJ.H. Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT) Investigators Amiodarone or an implantable cardioverter-defibrillator for congestive heart failure.N. Engl. J. Med.2005352322523710.1056/NEJMoa04339915659722
     [Google Scholar]
  38. ClelandJ.G.F. DaubertJ.C. ErdmannE. FreemantleN. GrasD. KappenbergerL. TavazziL. Cardiac Resynchronization-Heart Failure (CARE-HF) Study Investigators The effect of cardiac resynchronization on morbidity and mortality in heart failure.N. Engl. J. Med.2005352151539154910.1056/NEJMoa05049615753115
     [Google Scholar]
  39. DaubertC. GoldM.R. AbrahamW.T. GhioS. HassagerC. GoodeG. Szili-TörökT. LindeC. REVERSE Study Group Prevention of disease progression by cardiac resynchronization therapy in patients with asymptomatic or mildly symptomatic left ventricular dysfunction: Insights from the European cohort of the REVERSE (Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction) trial.J. Am. Coll. Cardiol.200954201837184610.1016/j.jacc.2009.08.01119800193
     [Google Scholar]
  40. BristowM.R. SaxonL.A. BoehmerJ. KruegerS. KassD.A. De MarcoT. CarsonP. DiCarloL. DeMetsD. WhiteB.G. DeVriesD.W. FeldmanA.M. Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure (COMPANION) Investigators Cardiac-resynchronization therapy with or without an implantable defibrillator in advanced chronic heart failure.N. Engl. J. Med.2004350212140215010.1056/NEJMoa03242315152059
     [Google Scholar]
  41. MossA.J. HallW.J. CannomD.S. KleinH. BrownM.W. DaubertJ.P. EstesN.A.M.III FosterE. GreenbergH. HigginsS.L. PfefferM.A. SolomonS.D. WilberD. ZarebaW. MADIT-CRT Trial Investigators Cardiac-resynchronization therapy for the prevention of heart-failure events.N. Engl. J. Med.2009361141329133810.1056/NEJMoa090643119723701
     [Google Scholar]
  42. BuiA.L. HorwichT.B. FonarowG.C. Epidemiology and risk profile of heart failure.Nat. Rev. Cardiol.201181304110.1038/nrcardio.2010.16521060326
     [Google Scholar]
  43. TimmisA. KazakiewiczD. TownsendN. HuculeciR. AboyansV. VardasP. Global epidemiology of acute coronary syndromes.Nat. Rev. Cardiol.2023201177878810.1038/s41569‑023‑00884‑037231077
     [Google Scholar]
  44. RogerV.L. The heart failure epidemic.Int. J. Environ. Res. Public Health2010741807183010.3390/ijerph704180720617060
     [Google Scholar]
  45. MoranA.E. ForouzanfarM.H. RothG.A. MensahG.A. EzzatiM. FlaxmanA. MurrayC.J.L. NaghaviM. The global burden of ischemic heart disease in 1990 and 2010: The Global Burden of Disease 2010 study.Circulation2014129141493150110.1161/CIRCULATIONAHA.113.00404624573351
     [Google Scholar]
  46. BenjaminE.J. ViraniS.S. CallawayC.W. ChamberlainA.M. ChangA.R. ChengS. ChiuveS.E. CushmanM. DellingF.N. DeoR. de FerrantiS.D. FergusonJ.F. FornageM. GillespieC. IsasiC.R. JiménezM.C. JordanL.C. JuddS.E. LacklandD. LichtmanJ.H. LisabethL. LiuS. LongeneckerC.T. LutseyP.L. MackeyJ.S. MatcharD.B. MatsushitaK. MussolinoM.E. NasirK. O’FlahertyM. PalaniappanL.P. PandeyA. PandeyD.K. ReevesM.J. RitcheyM.D. RodriguezC.J. RothG.A. RosamondW.D. SampsonU.K.A. SatouG.M. ShahS.H. SpartanoN.L. TirschwellD.L. TsaoC.W. VoeksJ.H. WilleyJ.Z. WilkinsJ.T. WuJ.H.Y. AlgerH.M. WongS.S. MuntnerP. American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics Subcommittee Heart disease and stroke statistics—2018 update: A report from the american heart association.Circulation201813712e67e49210.1161/CIR.000000000000055829386200
     [Google Scholar]
  47. BergJ. LindgrenP. KahanT. SchillO. PerssonH. EdnerM. MejhertM. Health-related quality of life and long-term morbidity and mortality in patients hospitalised with systolic heart failure.JRSM Cardiovasc. Dis.20143204800401454873510.1177/204800401454873525396054
     [Google Scholar]
  48. TownsendN. KazakiewiczD. Lucy WrightF. TimmisA. HuculeciR. TorbicaA. GaleC.P. AchenbachS. WeidingerF. VardasP. Epidemiology of cardiovascular disease in Europe.Nat. Rev. Cardiol.202219213314310.1038/s41569‑021‑00607‑334497402
     [Google Scholar]
  49. MusiałekP. MontaukL. SaugnetA. MicariA. HopkinsL.N. The cardio-vascular future of panvascular medicine: The basics.Kardiol. Pol.2019771089990110.33963/KP.1503431651911
     [Google Scholar]
  50. GheorghiadeM. AmbrosyA. One step forward, two steps back.Nat. Rev. Cardiol.201182727310.1038/nrcardio.2010.20521270845
     [Google Scholar]
  51. JarochaD. MilczarekO. KaweckiZ. WendrychowiczA. KwiatkowskiS. MajkaM. Preliminary study of autologous bone marrow nucleated cells transplantation in children with spinal cord injury.Stem Cells Transl. Med.20143339540410.5966/sctm.2013‑014124493853
     [Google Scholar]
  52. PäthG. PerakakisN. MantzorosC.S. SeufertJ. Stem cells in the treatment of diabetes mellitus — Focus on mesenchymal stem cells.Metabolism20199011510.1016/j.metabol.2018.10.00530342065
     [Google Scholar]
  53. SkoczekD. DulakJ. Kachamakova-TrojanowskaN. Maturity onset diabetes of the young—new approaches for disease modelling.Int. J. Mol. Sci.20212214755310.3390/ijms2214755334299172
     [Google Scholar]
  54. BraunwaldE. Cell-based therapy in cardiac regeneration.Circ. Res.2018123213213710.1161/CIRCRESAHA.118.31348429976683
     [Google Scholar]
  55. MenaschéP. Cell therapy trials for heart regeneration — Lessons learned and future directions.Nat. Rev. Cardiol.2018151165967110.1038/s41569‑018‑0013‑029743563
     [Google Scholar]
  56. AttarA. HosseinpourA. HosseinpourH. KazemiA. Major cardiovascular events after bone marrow mononuclear cell transplantation following acute myocardial infarction: An updated post-BAMI meta-analysis of randomized controlled trials.BMC Cardiovasc. Disord.202222125910.1186/s12872‑022‑02701‑x35681123
     [Google Scholar]
  57. FisherS.A. DoreeC. MathurA. TaggartD.P. Martin-RendonE. Stem cell therapy for chronic ischaemic heart disease and congestive heart failure.Cochrane Libr.2016201612CD00788810.1002/14651858.CD007888.pub328012165
     [Google Scholar]
  58. HosseinpourA. KheshtiF. KazemiA. AttarA. Comparing the effect of bone marrow mono-nuclear cells with mesenchymal stem cells after acute myocardial infarction on improvement of left ventricular function: A meta-analysis of clinical trials.Stem Cell Res. Ther.202213120310.1186/s13287‑022‑02883‑335578329
     [Google Scholar]
  59. LeeH. ChoH.J. HanY. LeeS.H. Mid- to long-term efficacy and safety of stem cell therapy for acute myocardial infarction: A systematic review and meta-analysis.Stem Cell Res. Ther.202415129010.1186/s13287‑024‑03891‑139256845
     [Google Scholar]
  60. DrabikL. MazurekA. Dzieciuch-RojekM. TekieliL. CzyżŁ. KwiecieńE. KułagaA. MikundaA. ChmielJ. PłazakW. RubiśP. MusiałekP. Trans-endocardial delivery of progenitor cells to compromised myocardium using the “needle technique”and risk of myocardial injury.Adv Interv Cardiol202218442343010.5114/aic.2022.12103336967845
     [Google Scholar]
  61. PuL. MengM. WuJ. ZhangJ. HouZ. GaoH. XuH. LiuB. TangW. JiangL. LiY. Compared to the amniotic membrane, Wharton’s jelly may be a more suitable source of mesenchymal stem cells for cardiovascular tissue engineering and clinical regeneration.Stem Cell Res. Ther.2017817210.1186/s13287‑017‑0501‑x28320452
     [Google Scholar]
  62. GyöngyösiM. HallerP.M. BlakeD.J. Martin RendonE. Meta-analysis of cell therapy studies in heart failure and acute myocardial infarction.Circ. Res.2018123230130810.1161/CIRCRESAHA.117.31130229976694
     [Google Scholar]
  63. GudeN.A. SussmanM.A. Cardiac regenerative therapy: Many paths to repair.Trends Cardiovasc. Med.202030633834310.1016/j.tcm.2019.08.00931515053
     [Google Scholar]
  64. RohaniL. JohnsonA.A. NaghshP. RancourtD.E. UlrichH. HollandH. Concise review: Molecular cytogenetics and quality control: Clinical guardians for pluripotent stem cells.Stem Cells Transl. Med.201871286787510.1002/sctm.18‑008730218497
     [Google Scholar]
  65. YamanakaS. Pluripotent stem cell-based cell therapy—promise and challenges.Cell Stem Cell202027452353110.1016/j.stem.2020.09.01433007237
     [Google Scholar]
  66. WuK.H. ZhouB. LuS.H. FengB. YangS.G. DuW.T. GuD.S. HanZ.C. LiuY.L. In vitro and in vivo differentiation of human umbilical cord derived stem cells into endothelial cells.J. Cell. Biochem.2007100360861610.1002/jcb.2107816960877
     [Google Scholar]
  67. WangH.S. HungS.C. PengS.T. HuangC.C. WeiH.M. GuoY.J. FuY.S. LaiM.C. ChenC.C. Mesenchymal stem cells in the Wharton’s jelly of the human umbilical cord.Stem Cells20042271330133710.1634/stemcells.2004‑001315579650
     [Google Scholar]
  68. NekantiU. RaoV.B. BahirvaniA.G. JanM. ToteyS. TaM. Long-term expansion and pluripotent marker array analysis of Wharton’s jelly-derived mesenchymal stem cells.Stem Cells Dev.201019111713010.1089/scd.2009.017719619003
     [Google Scholar]
  69. GaoL.R. ZhangN.K. DingQ.A. ChenH.Y. HuX. JiangS. LiT.C. ChenY. WangZ.G. YeY. ZhuZ.M. Common expression of stemness molecular markers and early cardiac transcription factors in human Wharton’s jelly-derived mesenchymal stem cells and embryonic stem cells.Cell Transplant.201322101883190010.3727/096368912X66244423394400
     [Google Scholar]
  70. Musiał-WysockaA. KotM. SułkowskiM. BadyraB. MajkaM. Molecular and functional verification of wharton’s jelly mesenchymal stem cells (WJ-MSCs) pluripotency.Int. J. Mol. Sci.2019208180710.3390/ijms2008180731013696
     [Google Scholar]
  71. HsiehJ.Y. WangH.W. ChangS.J. LiaoK.H. LeeI.H. LinW.S. WuC.H. LinW.Y. ChengS.M. Mesenchymal stem cells from human umbilical cord express preferentially secreted factors related to neuroprotection, neurogenesis, and angiogenesis.PLoS One201388e7260410.1371/journal.pone.007260423991127
     [Google Scholar]
  72. RanganathS.H. LevyO. InamdarM.S. KarpJ.M. Harnessing the mesenchymal stem cell secretome for the treatment of cardiovascular disease.Cell Stem Cell201210324425810.1016/j.stem.2012.02.00522385653
     [Google Scholar]
  73. DrobiovaH. SindhuS. AhmadR. HaddadD. Al-MullaF. Al MadhounA. Wharton’s jelly mesenchymal stem cells: A concise review of their secretome and prospective clinical applications.Front. Cell Dev. Biol.202311121121710.3389/fcell.2023.121121737440921
     [Google Scholar]
  74. LyuY. XieJ. LiuY. XiaoM. LiY. YangJ. YangJ. LiuW. Injectable hyaluronic acid hydrogel loaded with functionalized human mesenchymal stem cell aggregates for repairing infarcted myocardium.ACS Biomater. Sci. Eng.20206126926693710.1021/acsbiomaterials.0c0134433320638
     [Google Scholar]
  75. AbbaszadehH. GhorbaniF. DerakhshaniM. MovassaghpourA.A. YousefiM. TalebiM. ShamsasenjanK. Regenerative potential of Wharton’s jelly‐derived mesenchymal stem cells: A new horizon of stem cell therapy.J. Cell. Physiol.2020235129230924010.1002/jcp.2981032557631
     [Google Scholar]
  76. CharronD. Suberbielle-BoisselC. Al-DaccakR. Immunogenicity and allogenicity: A challenge of stem cell therapy.J. Cardiovasc. Transl. Res.20092113013810.1007/s12265‑008‑9062‑920559977
     [Google Scholar]
  77. CovasD.T. PanepucciR.A. FontesA.M. SilvaW.A.Jr OrellanaM.D. FreitasM.C.C. NederL. SantosA.R.D. PeresL.C. JamurM.C. ZagoM.A. Multipotent mesenchymal stromal cells obtained from diverse human tissues share functional properties and gene-expression profile with CD146+ perivascular cells and fibroblasts.Exp. Hematol.200836564265410.1016/j.exphem.2007.12.01518295964
     [Google Scholar]
  78. MusialekP. MazurekA. JarochaD. TekieliL. SzotW. KostkiewiczM. BanysR.P. UrbanczykM. KadzielskiA. TrystulaM. KijowskiJ. ZmudkaK. PodolecP. MajkaM. Myocardial regeneration strategy using Wharton’s jelly mesenchymal stem cells as an off-the-shelf ‘unlimited’ therapeutic agent: Results from the acute myocardial infarction first-in-man study.Adv Interv Cardiol20152210010710.5114/pwki.2015.5228226161101
     [Google Scholar]
  79. HothamW.E. HensonF.M.D. The use of large animals to facilitate the process of MSC going from laboratory to patient—‘bench to bedside’.Cell Biol. Toxicol.202036210311410.1007/s10565‑020‑09521‑932206986
     [Google Scholar]
  80. OrbayH. TobitaM. MizunoH. Mesenchymal stem cells isolated from adipose and other tissues: Basic biological properties and clinical applications.Stem Cells Int.201220121910.1155/2012/46171822666271
     [Google Scholar]
  81. MajkaM. SułkowskiM. BadyraB. MusiałekP. Concise review: Mesenchymal stem cells in cardiovascular regeneration: Emerging research directions and clinical applications.Stem Cells Transl. Med.20176101859186710.1002/sctm.16‑048428836732
     [Google Scholar]
  82. FriedensteinA.J. ChailakhjanR.K. LalykinaK.S. The development of fibroblast colonies in monolayer cultures of guinea-pig bone marrow and spleen cells.Cell Prolif.19703439340310.1111/j.1365‑2184.1970.tb00347.x5523063
     [Google Scholar]
  83. FriedensteinA.J. ChailakhyanR.K. LatsinikN.V. PanasyukA.F. Keiliss-BorokI.V. Stromal cells responsible for transferring the microenvironment of the hemopoietic tissues. Cloning in vitro and retransplantation in vivo.Transplantation197417433134010.1097/00007890‑197404000‑000014150881
     [Google Scholar]
  84. BatsaliA.K. KastrinakiM.C. PapadakiH.A. PontikoglouC. Mesenchymal stem cells derived from Wharton’s Jelly of the umbilical cord: Biological properties and emerging clinical applications.Curr. Stem Cell Res. Ther.20138214415510.2174/1574888X1130802000523279098
     [Google Scholar]
  85. AmableP.R. TeixeiraM.V.T. CariasR.B.V. GranjeiroJ.M. BorojevicR. Protein synthesis and secretion in human mesenchymal cells derived from bone marrow, adipose tissue and Wharton’s jelly.Stem Cell Res. Ther.2014525310.1186/scrt44224739658
     [Google Scholar]
  86. ZukP.A. ZhuM. MizunoH. HuangJ. FutrellJ.W. KatzA.J. BenhaimP. LorenzH.P. HedrickM.H. Multilineage cells from human adipose tissue: Implications for cell-based therapies.Tissue Eng.20017221122810.1089/10763270130006285911304456
     [Google Scholar]
  87. GriffithsM.J.D. BonnetD. JanesS.M. Stem cells of the alveolar epithelium.Lancet2005366948124926010.1016/S0140‑6736(05)66916‑416023517
     [Google Scholar]
  88. De BariC. Dell’AccioF. TylzanowskiP. LuytenF.P. Multipotent mesenchymal stem cells from adult human synovial membrane.Arthritis Rheum.20014481928194210.1002/1529‑0131(200108)44:8<1928::AID‑ART331>3.0.CO;2‑P11508446
     [Google Scholar]
  89. GronthosS. MankaniM. BrahimJ. RobeyP.G. ShiS. Postnatal human dental pulp stem cells (DPSCs) in vitro and in vivo .Proc. Natl. Acad. Sci. USA20009725136251363010.1073/pnas.24030979711087820
     [Google Scholar]
  90. MiaoZ. JinJ. ChenL. ZhuJ. HuangW. ZhaoJ. QianH. ZhangX. Isolation of mesenchymal stem cells from human placenta: Comparison with human bone marrow mesenchymal stem cells.Cell Biol. Int.200630968168710.1016/j.cellbi.2006.03.00916870478
     [Google Scholar]
  91. TroyerD.L. WeissM.L. Wharton’s jelly-derived cells are a primitive stromal cell population.Stem Cells200826359159910.1634/stemcells.2007‑043918065397
     [Google Scholar]
  92. KimD.W. StaplesM. ShinozukaK. PantchevaP. KangS.D. BorlonganC. Wharton’s jelly-derived mesenchymal stem cells: Phenotypic characterization and optimizing their therapeutic potential for clinical applications.Int. J. Mol. Sci.2013146116921171210.3390/ijms14061169223727936
     [Google Scholar]
  93. KarahuseyinogluS. KocaefeC. BalciD. ErdemliE. CanA. Functional structure of adipocytes differentiated from human umbilical cord stroma-derived stem cells.Stem Cells200826368269110.1634/stemcells.2007‑073818192234
     [Google Scholar]
  94. NanaevA.K. KohnenG. MilovanovA.P. DomogatskyS.P. KaufmannP. Stromal differentiation and architecture of the human umbilical cord.Placenta1997181536410.1016/S0143‑4004(97)90071‑09032810
     [Google Scholar]
  95. CorotchiM.C. PopaM.A. RemesA. SimaL.E. GussiI. Lupu PlesuM. Isolation method and xeno-free culture conditions influence multipotent differentiation capacity of human Wharton’s jelly-derived mesenchymal stem cells.Stem Cell Res. Ther.2013448110.1186/scrt23223845279
     [Google Scholar]
  96. Regulation (EC) No 1394/2007 of the European Parliament and of the Council of 13 November 2007 on advanced therapy medicinal products and amending Directive 2001/83/EC and Regulation (EC) No 726/2004.2004Available from: http://data.europa.eu/eli/reg/2007/1394/2019-07-26
  97. BongsoA. FongC.Y. The therapeutic potential, challenges and future clinical directions of stem cells from the Wharton’s jelly of the human umbilical cord.Stem Cell Rev.20139222624010.1007/s12015‑012‑9418‑z23233233
     [Google Scholar]
  98. TangQ. ChenQ. LaiX. LiuS. ChenY. ZhengZ. XieQ. MaldonadoM. CaiZ. QinS. HoG. MaL. Malignant transformation potentials of human umbilical cord mesenchymal stem cells both spontaneously and via 3-methycholanthrene induction.PLoS One2013812e8184410.1371/journal.pone.008184424339974
     [Google Scholar]
  99. ChenG. YueA. RuanZ. YinY. WangR. RenY. ZhuL. Human umbilical cord-derived mesenchymal stem cells do not undergo malignant transformation during long-term culturing in serum-free medium.PLoS One201496e9856510.1371/journal.pone.009856524887492
     [Google Scholar]
  100. RatajczakM.Z. BujkoK. WojakowskiW. Stem cells and clinical practice: New advances and challenges at the time of emerging problems with induced pluripotent stem cell therapies.Pol Arch Intern Med20161261187989010.20452/pamw.364427906881
     [Google Scholar]
  101. LiM. NgS. Potentiating the naturally occurring process for repair of damaged heart.Curr. Pharm. Des.201420121950196310.2174/1381612811319999044723844738
     [Google Scholar]
  102. DominiciM. Le BlancK. MuellerI. Slaper-CortenbachI. MariniF.C. KrauseD.S. DeansR.J. KeatingA. ProckopD.J. HorwitzE.M. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement.Cytotherapy20068431531710.1080/1465324060085590516923606
     [Google Scholar]
  103. WeissM.L. AndersonC. MedicettyS. SeshareddyK.B. WeissR.J. VanderWerffI. TroyerD. McIntoshK.R. Immune properties of human umbilical cord Wharton’s jelly-derived cells.Stem Cells200826112865287410.1634/stemcells.2007‑102818703664
     [Google Scholar]
  104. ZhangW. LiuX.C. YangL. ZhuD.L. ZhangY.D. ChenY. ZhangH.Y. Wharton’s jelly-derived mesenchymal stem cells promote myocardial regeneration and cardiac repair after miniswine acute myocardial infarction.Coron. Artery Dis.201324754955810.1097/MCA.0b013e3283640f0023892469
     [Google Scholar]
  105. SubramanianA. FongC.Y. BiswasA. BongsoA. Comparative characterization of cells from the various compartments of the human umbilical cord shows that the wharton’s jelly compartment provides the best source of clinically utilizable mesenchymal stem cells.PLoS One2015106e012799210.1371/journal.pone.012799226061052
     [Google Scholar]
  106. CorraoS. La RoccaG. Lo IaconoM. ZummoG. GerbinoA. FarinaF. AnzaloneR. New frontiers in regenerative medicine in cardiology: The potential of Wharton’s jelly mesenchymal stem cells.Curr. Stem Cell Res. Ther.201381394510.2174/1574888X1130801000623278911
     [Google Scholar]
  107. MeyersonM. Role of telomerase in normal and cancer cells.J. Clin. Oncol.200018132626263410.1200/JCO.2000.18.13.262610893296
     [Google Scholar]
  108. BakshD. SongL. TuanR.S. Adult mesenchymal stem cells: Characterization, differentiation, and application in cell and gene therapy.J. Cell. Mol. Med.20048330131610.1111/j.1582‑4934.2004.tb00320.x15491506
     [Google Scholar]
  109. WagnerW. Implications of long-term culture for mesenchymal stem cells: Genetic defects or epigenetic regulation?Stem Cell Res. Ther.2012365410.1186/scrt14523257053
     [Google Scholar]
  110. SerakinciN. ChristensenR. GraakjaerJ. CairneyC.J. KeithW.N. AlsnerJ. SaretzkiG. KolvraaS. Ectopically hTERT expressing adult human mesenchymal stem cells are less radiosensitive than their telomerase negative counterpart.Exp. Cell Res.200731351056106710.1016/j.yexcr.2007.01.00217274981
     [Google Scholar]
  111. DrelaK. SarnowskaA. SiedleckaP. Szablowska-GadomskaI. WielgosM. JurgaM. LukomskaB. Domanska-JanikK. Low oxygen atmosphere facilitates proliferation and maintains undifferentiated state of umbilical cord mesenchymal stem cells in an hypoxia inducible factor-dependent manner.Cytotherapy201416788189210.1016/j.jcyt.2014.02.00924726658
     [Google Scholar]
  112. LupuM. KhalilM. AndreiE. IordacheF. PfannkucheK. NeefK. GeorgescuA. BuzilaC. BrockmeierK. ManiuH. HeschelerJ. Integration properties of Wharton’s jelly-derived novel mesenchymal stem cells into ventricular slices of murine hearts.Cell. Physiol. Biochem.2011281637610.1159/00033171421865849
     [Google Scholar]
  113. TaapkenS.M. NislerB.S. NewtonM.A. Sampsell-BarronT.L. LeonhardK.A. McIntireE.M. MontgomeryK.D. Karyotypic abnormalities in human induced pluripotent stem cells and embryonic stem cells.Nat. Biotechnol.201129431331410.1038/nbt.183521478842
     [Google Scholar]
  114. LundR.J. NärväE. LahesmaaR. Genetic and epigenetic stability of human pluripotent stem cells.Nat. Rev. Genet.2012131073274410.1038/nrg327122965355
     [Google Scholar]
  115. RebuzziniP. ZuccottiM. RediC.A. GaragnaS. Achilles’ heel of pluripotent stem cells: Genetic, genomic and epigenetic variations during prolonged culture.Cell. Mol. Life Sci.201673132453246610.1007/s00018‑016‑2171‑826961132
     [Google Scholar]
  116. ChoS. DischerD.E. LeongK.W. Vunjak-NovakovicG. WuJ.C. Challenges and opportunities for the next generation of cardiovascular tissue engineering.Nat. Methods20221991064107110.1038/s41592‑022‑01591‑336064773
     [Google Scholar]
  117. BerndtR. AlbrechtM. RuschR. Strategies to overcome the barrier of ischemic microenvironment in cell therapy of cardiovascular disease.Int. J. Mol. Sci.2021225231210.3390/ijms2205231233669136
     [Google Scholar]
  118. Le BlancK. TammikC. RosendahlK. ZetterbergE. RingdénO. HLA expression and immunologic propertiesof differentiated and undifferentiated mesenchymal stem cells.Exp. Hematol.2003311089089610.1016/S0301‑472X(03)00110‑314550804
     [Google Scholar]
  119. RyanJ.M. BarryF.P. MurphyJ.M. MahonB.P. Mesenchymal stem cells avoid allogeneic rejection.J. Inflamm.200521810.1186/1476‑9255‑2‑816045800
     [Google Scholar]
  120. AmableP.R. TeixeiraM.V.T. CariasR.B.V. GranjeiroJ.M. BorojevicR. Gene expression and protein secretion during human mesenchymal cell differentiation into adipogenic cells.BMC Cell Biol.20141514610.1186/s12860‑014‑0046‑0
     [Google Scholar]
  121. DingD.C. ChouH.L. ChangY.H. HungW.T. LiuH.W. ChuT.Y. Characterization of HLA-G and related immunosuppressive effects in human umbilical cord stroma-derived stem cells.Cell Transplant.201625221722810.3727/096368915X68818226044082
     [Google Scholar]
  122. SwamynathanP. VenugopalP. KannanS. ThejC. KolkundarU. BhagwatS. TaM. MajumdarA.S. BalasubramanianS. Are serum-free and xeno-free culture conditions ideal for large scale clinical grade expansion of Wharton’s jelly derived mesenchymal stem cells? A comparative study.Stem Cell Res. Ther.2014548810.1186/scrt47725069491
     [Google Scholar]
  123. NovotnyG.E. GnothC. Variability of fibroblast morphology in vivo: A silver impregnation study on human digital dermis and subcutis.J. Anat.19911771952071769894
     [Google Scholar]
  124. McelreaveyK.D. IrvineA. EnnisK.T. McleanW.H.I. Isolation, culture and characterisation of fibroblast-like cells derived from the Wharton’s jelly portion of human umbilical cord.Biochem. Soc. Trans.199119129S10.1042/bst019029s1709890
     [Google Scholar]
  125. GaafarT. AttiaW. MahmoudS. SabryD. AzizO.A. RasheedD. HamzaH. Cardioprotective effects of wharton jelly derived mesenchymal stem cell transplantation in a rodent model of myocardial injury.Int. J. Stem Cells2017101485910.15283/ijsc1606328446005
     [Google Scholar]
  126. RavikanthM. SoujanyaP. ManjunathK. SaraswathiT.R. RamachandranC.R. Heterogenecity of fibroblasts.J. Oral Maxillofac. Pathol.201115224725010.4103/0973‑029X.8451622529592
     [Google Scholar]
  127. HeoJ.S. ChoiY. KimH.S. KimH.O. Comparison of molecular profiles of human mesenchymal stem cells derived from bone marrow, umbilical cord blood, placenta and adipose tissue.Int. J. Mol. Med.201637111512510.3892/ijmm.2015.241326719857
     [Google Scholar]
  128. NingH. LinG. LueT.F. LinC.S. Mesenchymal stem cell marker Stro-1 is a 75kd endothelial antigen.Biochem. Biophys. Res. Commun.2011413235335710.1016/j.bbrc.2011.08.10421903091
     [Google Scholar]
  129. MirotsouM. JayawardenaT.M. SchmeckpeperJ. GnecchiM. DzauV.J. Paracrine mechanisms of stem cell reparative and regenerative actions in the heart.J. Mol. Cell. Cardiol.201150228028910.1016/j.yjmcc.2010.08.00520727900
     [Google Scholar]
  130. ChoiM. LeeH.S. NaidansarenP. KimH.K. OE. ChaJ.H. AhnH.Y. YangP.I. ShinJ.C. JoeY.A. Proangiogenic features of Wharton’s jelly-derived mesenchymal stromal/stem cells and their ability to form functional vessels.Int. J. Biochem. Cell Biol.201345356057010.1016/j.biocel.2012.12.00123246593
     [Google Scholar]
  131. LiuS. YuanM. HouK. ZhangL. ZhengX. ZhaoB. SuiX. XuW. LuS. GuoQ. Immune characterization of mesenchymal stem cells in human umbilical cord Wharton’s jelly and derived cartilage cells.Cell. Immunol.20122781-2354410.1016/j.cellimm.2012.06.01023121974
     [Google Scholar]
  132. ShenW.C. LiangC.J. WuV.C. WangS.H. YoungG.H. LaiI.R. ChienC.L. WangS.M. WuK.D. ChenY.L. Endothelial progenitor cells derived from Wharton’s jelly of the umbilical cord reduces ischemia-induced hind limb injury in diabetic mice by inducing HIF-1α/IL-8 expression.Stem Cells Dev.20132291408141810.1089/scd.2012.044523252631
     [Google Scholar]
  133. GuoJ. LinG. BaoC. HuZ. HuM. Anti-inflammation role for mesenchymal stem cells transplantation in myocardial infarction.Inflammation2007303-49710410.1007/s10753‑007‑9025‑317497204
     [Google Scholar]
  134. ZayedS.A. GaafarT.M. SamyR.M. SabryD. NasrA.S. MaksoudF.A.A. Production of endothelial progenitor cells obtained from human Wharton’s jelly using different culture conditions.Biotech. Histochem.201691853253910.1080/10520295.2016.125028427849398
     [Google Scholar]
  135. RammalH. HarmouchC. MaertenC. GaucherC. BoulmedaisF. SchaafP. VoegelJ.C. Laurent-MaquinD. MenuP. KerdjoudjH. Upregulation of endothelial gene markers in Wharton’s jelly mesenchymal stem cells cultured on polyelectrolyte multilayers.J. Biomed. Mater. Res. A2017105129230010.1002/jbm.a.3586827797148
     [Google Scholar]
  136. WuK.H. ZhouB. YuC.T. CuiB. LuS.H. HanZ.C. LiuY.L. Therapeutic potential of human umbilical cord derived stem cells in a rat myocardial infarction model.Ann. Thorac. Surg.20078341491149810.1016/j.athoracsur.2006.10.06617383364
     [Google Scholar]
  137. NascimentoD.S. MosqueiraD. SousaL.M. TeixeiraM. FilipeM. ResendeT.P. AraújoA.F. ValenteM. AlmeidaJ. MartinsJ.P. SantosJ.M. BárciaR.N. CruzP. CruzH. Pinto-do-ÓP. 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.201451510.1186/scrt39424411922
     [Google Scholar]
  138. YannarelliG. DayanV. PacienzaN. LeeC.J. MedinJ. KeatingA. Human umbilical cord perivascular cells exhibit enhanced cardiomyocyte reprogramming and cardiac function after experimental acute myocardial infarction.Cell Transplant.20132291651166610.3727/096368912X65767523043977
     [Google Scholar]
  139. LiuC.B. HuangH. SunP. Human umbilical cord-derived mesenchymal stromal cells improve left ventricular function, perfusion, and remodeling in a porcine model of chronic myocardial ischemia stem cells.Transl Med.20165810041013
     [Google Scholar]
  140. ZhangC. ZhouG. ChenY. LiuS. ChenF. XieL. WangW. ZhangY. WangT. LaiX. MaL. Human umbilical cord mesenchymal stem cells alleviate interstitial fibrosis and cardiac dysfunction in a dilated cardiomyopathy rat model by inhibiting TNF‑α and TGF‑β1/ERK1/2 signaling pathways.Mol. Med. Rep.2018171717829115435
     [Google Scholar]
  141. QiuY. YunM.M. HanX. ZhaoR. ZhouE. YunS. Human umbilical cord mesenchymal stromal cells suppress MHC class II expression on rat vascular endothelium and prolong survival time of cardiac allograft.Int. J. Clin. Exp. Med.2014771760176725126177
     [Google Scholar]
  142. WangY. ChenX. CaoW. ShiY. Plasticity of mesenchymal stem cells in immunomodulation: Pathological and therapeutic implications.Nat. Immunol.201415111009101610.1038/ni.300225329189
     [Google Scholar]
  143. MaY. YabluchanskiyA. IyerR.P. CannonP.L. FlynnE.R. JungM. HenryJ. CatesC.A. Deleon-PennellK.Y. LindseyM.L. Temporal neutrophil polarization following myocardial infarction.Cardiovasc. Res.20161101516110.1093/cvr/cvw02426825554
     [Google Scholar]
  144. ArutyunyanI. ElchaninovA. MakarovA. FatkhudinovT. Umbilical cord as prospective source for mesenchymal stem cell‐based therapy.Stem Cells Int.201620161690128610.1155/2016/690128627651799
     [Google Scholar]
  145. ChatterjeeD. MarquardtN. TufaD.M. HatlapatkaT. HassR. KasperC. von KaisenbergC. SchmidtR.E. JacobsR. Human umbilical cord-derived mesenchymal stem cells utilize activin-a to suppress interferon-î³ production by natural killer cells.Front. Immunol.2014566210.3389/fimmu.2014.0066225584044
     [Google Scholar]
  146. ChoiY.J. KooJ.B. KimH.Y. SeoJ.W. LeeE.J. KimW.R. ChoJ.Y. HahmK.B. HongS.P. KimD.H. YooJ.H. Umbilical cord/placenta-derived mesenchymal stem cells inhibit fibrogenic activation in human intestinal myofibroblasts via inhibition of myocardin-related transcription factor A.Stem Cell Res. Ther.201910129110.1186/s13287‑019‑1385‑831547873
     [Google Scholar]
  147. DondersR. VanheusdenM. BogieJ.F.J. RavanidisS. ThewissenK. StinissenP. GyselaersW. HendriksJ.J.A. HellingsN. Human wharton’s jelly-derived stem cells display immunomodulatory properties and transiently improve rat experimental autoimmune encephalomyelitis.Cell Transplant.201524102077209810.3727/096368914X68510425310756
     [Google Scholar]
  148. TipnisS. ViswanathanC. MajumdarA.S. Immunosuppressive properties of human umbilical cord‐derived mesenchymal stem cells: Role of B7‐H1 and IDO.Immunol. Cell Biol.201088879580610.1038/icb.2010.4720386557
     [Google Scholar]
  149. ZhouC. YangB. TianY. JiaoH. ZhengW. WangJ. GuanF. Immunomodulatory effect of human umbilical cord Wharton’s jelly-derived mesenchymal stem cells on lymphocytes.Cell. Immunol.20112721333810.1016/j.cellimm.2011.09.01022004796
     [Google Scholar]
  150. LiangC.J. ShenW.C. ChangF.B. WuV.C. WangS.H. YoungG.H. TsaiJ.S. TsengY.C. PengY.S. ChenY.L. Endothelial progenitor cells derived from wharton’s jelly of human umbilical cord attenuate ischemic acute kidney injury by increasing vascularization and decreasing apoptosis, inflammation, and fibrosis.Cell Transplant.20152471363137710.3727/096368914X68172024819279
     [Google Scholar]
  151. LimM. WangW. LiangL. HanZ. LiZ. GengJ. ZhaoM. JiaH. FengJ. WeiZ. SongB. ZhangJ. LiJ. LiuT. WangF. LiT. LiJ. FangY. GaoJ. HanZ. Intravenous injection of allogeneic umbilical cord-derived multipotent mesenchymal stromal cells reduces the infarct area and ameliorates cardiac function in a porcine model of acute myocardial infarction.Stem Cell Res. Ther.20189112910.1186/s13287‑018‑0888‑z29751831
     [Google Scholar]
  152. IbáñezB. HeuschG. OvizeM. Van de WerfF. Evolving therapies for myocardial ischemia/reperfusion injury.J. Am. Coll. Cardiol.201565141454147110.1016/j.jacc.2015.02.03225857912
     [Google Scholar]
  153. ReineckeH. MinamiE. ZhuW.Z. LaflammeM.A. Cardiogenic differentiation and transdifferentiation of progenitor cells.Circ. Res.2008103101058107110.1161/CIRCRESAHA.108.18058818988903
     [Google Scholar]
  154. AndreadouI. Cabrera-FuentesH.A. DevauxY. FrangogiannisN.G. FrantzS. GuzikT. LiehnE.A. GomesC.P.C. SchulzR. HausenloyD.J. Immune cells as targets for cardioprotection: New players and novel therapeutic opportunities.Cardiovasc. Res.201911571117113010.1093/cvr/cvz05030825305
     [Google Scholar]
  155. JenningsR.B. MurryC.E. SteenbergenC.Jr ReimerK.A. Development of cell injury in sustained acute ischemia.Circulation1990823Suppl.II2II122394018
     [Google Scholar]
  156. ZhaoB.H. RuzeA. ZhaoL. LiQ.L. TangJ. XiefukaitiN. GaiM.T. DengA.X. ShanX.F. GaoX.M. The role and mechanisms of microvascular damage in the ischemic myocardium.Cell. Mol. Life Sci.2023801134110.1007/s00018‑023‑04998‑z37898977
     [Google Scholar]
  157. ShindeA.V. FrangogiannisN.G. Fibroblasts in myocardial infarction: A role in inflammation and repair.J. Mol. Cell. Cardiol.201470748210.1016/j.yjmcc.2013.11.01524321195
     [Google Scholar]
  158. Barrère-LemaireS. VincentA. JorgensenC. PiotC. NargeotJ. DjouadF. Mesenchymal stromal cells for improvement of cardiac function following acute myocardial infarction: A matter of timing.Physiol. Rev.2024104265972510.1152/physrev.00009.202337589393
     [Google Scholar]
  159. Vieira PaladinoF. de Moraes RodriguesJ. da SilvaA. GoldbergA.C. The immunomodulatory potential of wharton’s jelly mesenchymal stem/stromal cells.Stem Cells Int.201920191710.1155/2019/354891731281372
     [Google Scholar]
  160. RaziyevaK. KimY. ZharkinbekovZ. TemirkhanovaK. SaparovA. Novel therapies for the treatment of cardiac fibrosis following myocardial infarction.Biomedicines2022109217810.3390/biomedicines1009217836140279
     [Google Scholar]
  161. ReimerK.A. JenningsR.B. TatumA.H. Pathobiology of acute myocardial ischemia: Metabolic, functional and ultrastructural studies.Am. J. Cardiol.1983522728110.1016/0002‑9149(83)90180‑76869259
     [Google Scholar]
  162. KlonerR.A. RudeR.E. CarlsonN. MarokoP.R. DeBoerL.W. BraunwaldE. Ultrastructural evidence of microvascular damage and myocardial cell injury after coronary artery occlusion: which comes first?Circulation198062594595210.1161/01.CIR.62.5.9457418179
     [Google Scholar]
  163. OrogoA.M. GustafssonÅ.B. Cell death in the myocardium: My heart won’t go on.IUBMB Life201365865165610.1002/iub.118023824949
     [Google Scholar]
  164. HuangC. AndresA.M. RatliffE.P. HernandezG. LeeP. GottliebR.A. Preconditioning involves selective mitophagy mediated by Parkin and p62/SQSTM1.PLoS One201166e2097510.1371/journal.pone.002097521687634
     [Google Scholar]
  165. ZhouW. YuanJ. SnapShot: Necroptosis.Cell20141582464464.e110.1016/j.cell.2014.06.04125036639
     [Google Scholar]
  166. OerlemansM.I.F.J. KoudstaalS. ChamuleauS.A. de KleijnD.P. DoevendansP.A. SluijterJ.P.G. Targeting cell death in the reperfused heart: Pharmacological approaches for cardioprotection.Int. J. Cardiol.2013165341042210.1016/j.ijcard.2012.03.05522459400
     [Google Scholar]
  167. WuM.Y. YiangG.T. LiaoW.T. TsaiA.P.Y. ChengY.L. ChengP.W. LiC.Y. LiC.J. Current mechanistic concepts in ischemia and reperfusion injury.Cell. Physiol. Biochem.20184641650166710.1159/00048924129694958
     [Google Scholar]
  168. VilahurG. Juan-BabotO. PeñaE. OñateB. CasaníL. BadimonL. Molecular and cellular mechanisms involved in cardiac remodeling after acute myocardial infarction.J. Mol. Cell. Cardiol.201150352253310.1016/j.yjmcc.2010.12.02121219908
     [Google Scholar]
  169. BuggerH. PfeilK. Mitochondrial ROS in myocardial ischemia reperfusion and remodeling.Biochim. Biophys. Acta Mol. Basis Dis.20201866716576810.1016/j.bbadis.2020.16576832173461
     [Google Scholar]
  170. LeoniG. SoehnleinO. (Re) Solving repair after myocardial infarction.Front. Pharmacol.20189134210.3389/fphar.2018.0134230534069
     [Google Scholar]
  171. MaY. IyerR.P. JungM. CzubrytM.P. LindseyM.L. Cardiac fibroblast activation post-myocardial infarction: Current knowledge gaps.Trends Pharmacol. Sci.201738544845810.1016/j.tips.2017.03.00128365093
     [Google Scholar]
  172. VargasS.O. SampsonB.A. SchoenF.J. Pathologic detection of early myocardial infarction: A critical review of the evolution and usefulness of modern techniques.Mod. Pathol.199912663564510392641
     [Google Scholar]
  173. Ben-MordechaiT. HolbovaR. Landa-RoubenN. Harel-AdarT. FeinbergM.S. Abd ElrahmanI. BlumG. EpsteinF.H. SilmanZ. CohenS. LeorJ. Macrophage subpopulations are essential for infarct repair with and without stem cell therapy.J. Am. Coll. Cardiol.201362201890190110.1016/j.jacc.2013.07.05723973704
     [Google Scholar]
  174. ZouggariY. Ait-OufellaH. BonninP. SimonT. SageA.P. GuérinC. VilarJ. CaligiuriG. TsiantoulasD. LauransL. DumeauE. KottiS. BrunevalP. CharoI.F. BinderC.J. DanchinN. TedguiA. TedderT.F. SilvestreJ.S. MallatZ. B lymphocytes trigger monocyte mobilization and impair heart function after acute myocardial infarction.Nat. Med.201319101273128010.1038/nm.328424037091
     [Google Scholar]
  175. JianY. ZhouX. ShanW. ChenC. GeW. CuiJ. YiW. SunY. Crosstalk between macrophages and cardiac cells after myocardial infarction.Cell Commun. Signal.202321110910.1186/s12964‑023‑01105‑437170235
     [Google Scholar]
  176. GuoQ.Y. YangJ.Q. FengX.X. ZhouY.J. Regeneration of the heart: From molecular mechanisms to clinical therapeutics.Mil. Med. Res.20231011810.1186/s40779‑023‑00452‑037098604
     [Google Scholar]
  177. MannD.L. Inflammatory mediators and the failing heart: Past, present, and the foreseeable future.Circ. Res.2002911198899810.1161/01.RES.0000043825.01705.1B12456484
     [Google Scholar]
  178. ChenW. FrangogiannisN.G. Fibroblasts in post-infarction inflammation and cardiac repair.Biochim. Biophys. Acta Mol. Cell Res.20131833494595310.1016/j.bbamcr.2012.08.02322982064
     [Google Scholar]
  179. FuX. KhalilH. KanisicakO. BoyerJ.G. VagnozziR.J. MalikenB.D. SargentM.A. PrasadV. Valiente-AlandiI. BlaxallB.C. MolkentinJ.D. Specialized fibroblast differentiated states underlie scar formation in the infarcted mouse heart.J. Clin. Invest.201812852127214310.1172/JCI9821529664017
     [Google Scholar]
  180. van den BorneS.W.M. DiezJ. BlankesteijnW.M. VerjansJ. HofstraL. NarulaJ. Myocardial remodeling after infarction: The role of myofibroblasts.Nat. Rev. Cardiol.201071303710.1038/nrcardio.2009.19919949426
     [Google Scholar]
  181. BainbridgeP. Wound healing and the role of fibroblasts.J. Wound Care2013228407412, 410-41210.12968/jowc.2013.22.8.40723924840
     [Google Scholar]
  182. PesceM. DudaG.N. ForteG. GiraoH. RayaA. Roca-CusachsP. SluijterJ.P.G. TschöpeC. Van LinthoutS. Cardiac fibroblasts and mechanosensation in heart development, health and disease.Nat. Rev. Cardiol.202320530932410.1038/s41569‑022‑00799‑236376437
     [Google Scholar]
  183. SavvatisK. van LinthoutS. MitevaK. PappritzK. WestermannD. SchefoldJ.C. FuschG. WeithäuserA. RauchU. BecherP.M. KlingelK. RingeJ. KurtzA. SchultheissH.P. TschöpeC. Mesenchymal stromal cells but not cardiac fibroblasts exert beneficial systemic immunomodulatory effects in experimental myocarditis.PLoS One201277e4104710.1371/journal.pone.004104722815907
     [Google Scholar]
  184. AguileraV. BriceñoL. ContrerasH. LampertiL. SepúlvedaE. Díaz-PerezF. LeónM. VeasC. MauraR. ToledoJ.R. FernándezP. CovarrubiasA. ZuñigaF.A. RadojkovicC. EscuderoC. AguayoC. Endothelium trans differentiated from Wharton’s jelly mesenchymal cells promote tissue regeneration: Potential role of soluble pro-angiogenic factors.PLoS One2014911e11102510.1371/journal.pone.011102525412260
     [Google Scholar]
  185. ArutyunyanI. FatkhudinovT. KananykhinaE. UsmanN. ElchaninovA. MakarovA. BolshakovaG. GoldshteinD. SukhikhG. Role of VEGF-A in angiogenesis promoted by umbilical cord-derived mesenchymal stromal/stem cells: In vitro study.Stem Cell Res. Ther.2016714610.1186/s13287‑016‑0305‑427001300
     [Google Scholar]
  186. AbumareeM.H. Al JumahM.A. KalionisB. JawdatD. Al KhaldiA. AbomarayF.M. FataniA.S. ChamleyL.W. KnawyB.A. Human placental mesenchymal stem cells (pMSCs) play a role as immune suppressive cells by shifting macrophage differentiation from inflammatory M1 to anti-inflammatory M2 macrophages.Stem Cell Rev.20139562064110.1007/s12015‑013‑9455‑223812784
     [Google Scholar]
  187. VadivelS. VincentP. SekaranS. Visaga AmbiS. MuralidarS. SelvarajV. PalaniappanB. ThirumalaiD. Inflammation in myocardial injury- Stem cells as potential immunomodulators for myocardial regeneration and restoration.Life Sci.202025011758210.1016/j.lfs.2020.11758232222465
     [Google Scholar]
  188. CorselloT. AmicoG. CorraoS. AnzaloneR. TimoneriF. Lo IaconoM. RussoE. SpatolaG.F. UzzoM.L. GiuffrèM. CaprndaM. KubatkaP. KruzliakP. ConaldiP.G. La RoccaG. Wharton’s jelly mesenchymal stromal cells from human umbilical cord: A close-up on immunomodulatory molecules featured in situ and in vitro.Stem Cell Rev. Rep.201915690091810.1007/s12015‑019‑09907‑131741193
     [Google Scholar]
  189. DanP. VelotÉ. FranciusG. MenuP. DecotV. Human-derived extracellular matrix from Wharton’s jelly: An untapped substrate to build up a standardized and homogeneous coating for vascular engineering.Acta Biomater.20174822723710.1016/j.actbio.2016.10.01827769940
     [Google Scholar]
  190. MaB. WangT. LiJ. WangQ. Extracellular matrix derived from Wharton’s Jelly-derived mesenchymal stem cells promotes angiogenesis via integrin αVβ3/c-Myc/P300/VEGF.Stem Cell Res. Ther.202213132710.1186/s13287‑022‑03009‑535851415
     [Google Scholar]
  191. ChinniciC.M. IannoloG. CittadiniE. CarrecaA.P. NascariD. TimoneriF. BellaM.D. CuscinoN. AmicoG. CarcioneC. ConaldiP.G. Extracellular vesicle-derived microRNAs of human Wharton’s jelly mesenchymal stromal cells may activate endogenous VEGF-A to promote angiogenesis.Int. J. Mol. Sci.2021224204510.3390/ijms2204204533669517
     [Google Scholar]
  192. de WitteS.F.H. LukF. Sierra ParragaJ.M. GargeshaM. MerinoA. KorevaarS.S. ShankarA.S. O’FlynnL. EllimanS.J. RoyD. BetjesM.G.H. NewsomeP.N. BaanC.C. HoogduijnM.J. Immunomodulation by therapeutic mesenchymal stromal cells (MSC) is triggered through phagocytosis of MSC by monocytic cells.Stem Cells201836460261510.1002/stem.277929341339
     [Google Scholar]
  193. ArnoA.I. Amini-NikS. BlitP.H. Al-ShehabM. BeloC. HererE. TienC.H. JeschkeM.G. Human Wharton’s jelly mesenchymal stem cells promote skin wound healing through paracrine signaling.Stem Cell Res. Ther.2014512810.1186/scrt41724564987
     [Google Scholar]
  194. Del BuonoM.G. GarmendiaC.M. SeropianI.M. GonzalezG. BerrocalD.H. Biondi-ZoccaiG. TrankleC.R. Bucciarelli-DucciC. ThieleH. LavieC.J. CreaF. AbbateA. Heart failure after st-elevation myocardial infarction: Beyond left ventricular adverse remodeling.Curr. Probl. Cardiol.202348810121510.1016/j.cpcardiol.2022.10121535460680
     [Google Scholar]
  195. MannD.L. BristowM.R. Mechanisms and models in heart failure: The biomechanical model and beyond.Circulation2005111212837284910.1161/CIRCULATIONAHA.104.50054615927992
     [Google Scholar]
  196. VatnerS.F. HittingerL. Coronary vascular mechanisms involved in decompensation from hypertrophy to heart failure.J. Am. Coll. Cardiol.1993224Suppl. AA34A4010.1016/0735‑1097(93)90460‑I8104205
     [Google Scholar]
  197. MissovE. CalzolariC. PauB. Circulating cardiac troponin I in severe congestive heart failure.Circulation19979692953295810.1161/01.CIR.96.9.29539386162
     [Google Scholar]
  198. ColucciW.S. Molecular and cellular mechanisms of myocardial failure.Am. J. Cardiol.1997801115L25L10.1016/S0002‑9149(97)00845‑X9412539
     [Google Scholar]
  199. SinghK. XiaoL. RemondinoA. SawyerD.B. ColucciW.S. Adrenergic regulation of cardiac myocyte apoptosis.J. Cell. Physiol.2001189325726510.1002/jcp.1002411748583
     [Google Scholar]
  200. GivertzM.M. ColucciW.S. New targets for heart-failure therapy: Endothelin, inflammatory cytokines, and oxidative stress.Lancet1998352Suppl. 1SI34SI3810.1016/S0140‑6736(98)90017‑49736478
     [Google Scholar]
  201. HunterJ.J. ChienK.R. Signaling pathways for cardiac hypertrophy and failure.N. Engl. J. Med.1999341171276128310.1056/NEJM19991021341170610528039
     [Google Scholar]
  202. SchironeL. ForteM. D’AmbrosioL. ValentiV. VecchioD. SchiavonS. SpinosaG. SartoG. PetrozzaV. FratiG. SciarrettaS. An overview of the molecular mechanisms associated with myocardial ischemic injury: State of the art and translational perspectives.Cells2022117116510.3390/cells1107116535406729
     [Google Scholar]
  203. RiehleC. BauersachsJ. Of mice and men: Models and mechanisms of diabetic cardiomyopathy.Basic Res. Cardiol.20191141210.1007/s00395‑018‑0711‑030443826
     [Google Scholar]
  204. HayashidaK. TakegawaR. ShoaibM. AokiT. ChoudharyR.C. KuschnerC.E. NishikimiM. MiyaraS.J. RolstonD.M. GuevaraS. KimJ. ShinozakiK. MolmentiE.P. BeckerL.B. Mitochondrial transplantation therapy for ischemia reperfusion injury: A systematic review of animal and human studies.J. Transl. Med.202119121410.1186/s12967‑021‑02878‑334001191
     [Google Scholar]
  205. SobolewskiK. MałkowskiA. BańkowskiE. JaworskiS. Wharton’s jelly as a reservoir of peptide growth factors.Placenta2005261074775210.1016/j.placenta.2004.10.00816226124
     [Google Scholar]
  206. BarrettA.N. FongC.Y. SubramanianA. LiuW. FengY. ChoolaniM. BiswasA. RajapakseJ.C. BongsoA. Human Wharton’s jelly mesenchymal stem cells show unique gene expression compared with bone marrow mesenchymal stem cells using single-cell RNA-sequencing.Stem Cells Dev.201928319621110.1089/scd.2018.013230484393
     [Google Scholar]
  207. WegmeyerH. BröskeA.M. LeddinM. KuentzerK. NisslbeckA.K. HupfeldJ. WiechmannK. KuhlenJ. von SchwerinC. SteinC. KnotheS. FunkJ. HussR. NeubauerM. Mesenchymal stromal cell characteristics vary depending on their origin.Stem Cells Dev.201322192606261810.1089/scd.2013.001623676112
     [Google Scholar]
  208. CaiB. TanX. ZhangY. LiX. WangX. ZhuJ. WangY. YangF. WangB. LiuY. XuC. PanZ. WangN. YangB. LuY. Mesenchymal stem cells and cardiomyocytes interplay to prevent myocardial hypertrophy.Stem Cells Transl. Med.20154121425143510.5966/sctm.2015‑003226586774
     [Google Scholar]
  209. CanA. KarahuseyinogluS. Concise review: Human umbilical cord stroma with regard to the source of fetus-derived stem cells.Stem Cells200725112886289510.1634/stemcells.2007‑041717690177
     [Google Scholar]
  210. MitchellK.E. WeissM.L. MitchellB.M. MartinP. DavisD. MoralesL. HelwigB. BeerenstrauchM. Abou-EasaK. HildrethT. TroyerD. MedicettyS. Matrix cells from Wharton’s jelly form neurons and glia.Stem Cells2003211506010.1634/stemcells.21‑1‑5012529551
     [Google Scholar]
  211. MaL. FengX.Y. CuiB.L. LawF. JiangX.W. YangL.Y. XieQ.D. HuangT.H. Human umbilical cord Wharton’s Jelly-derived mesenchymal stem cells differentiation into nerve-like cells.Chin. Med. J.2005118231987199316336835
     [Google Scholar]
  212. FuY.S. ChengY.C. LinM.Y.A. ChengH. ChuP.M. ChouS.C. ShihY.H. KoM.H. SungM.S. Conversion of human umbilical cord mesenchymal stem cells in Wharton’s jelly to dopaminergic neurons in vitro: Potential therapeutic application for Parkinsonism.Stem Cells200624111512410.1634/stemcells.2005‑005316099997
     [Google Scholar]
  213. ChaoK.C. ChaoK.F. FuY.S. LiuS.H. Islet-like clusters derived from mesenchymal stem cells in Wharton’s Jelly of the human umbilical cord for transplantation to control type 1 diabetes.PLoS One200831e145110.1371/journal.pone.000145118197261
     [Google Scholar]
  214. DengY. YiS. WangG. ChengJ. ZhangY. ChenW. TaiY. ChenS. ChenG. LiuW. ZhangQ. YangY. Umbilical cord-derived mesenchymal stem cells instruct dendritic cells to acquire tolerogenic phenotypes through the IL-6-mediated upregulation of SOCS1.Stem Cells Dev.201423172080209210.1089/scd.2013.055924730420
     [Google Scholar]
  215. NajarM. RaicevicG. BoufkerH.I. KazanH.F. BruynC.D. MeulemanN. BronD. ToungouzM. LagneauxL. Mesenchymal stromal cells use PGE2 to modulate activation and proliferation of lymphocyte subsets: Combined comparison of adipose tissue, Wharton’s Jelly and bone marrow sources.Cell. Immunol.2010264217117910.1016/j.cellimm.2010.06.00620619400
     [Google Scholar]
  216. RingdénO. UzunelM. RasmussonI. RembergerM. SundbergB. LönniesH. MarschallH.U. DlugoszA. SzakosA. HassanZ. OmazicB. AschanJ. BarkholtL. Le BlancK. Mesenchymal stem cells for treatment of therapy-resistant graft-versus-host disease.Transplantation200681101390139710.1097/01.tp.0000214462.63943.1416732175
     [Google Scholar]
  217. SoderR.P. DawnB. WeissM.L. DunavinN. WeirS. MitchellJ. LiM. ShuneL. SinghA.K. GangulyS. MorrisonM. AbdelhakimH. GodwinA.K. AbhyankarS. McGuirkJ. A phase I study to evaluate two doses of wharton’s jelly-derived mesenchymal stromal cells for the treatment of de novo high-risk or steroid-refractory acute graft versus host disease.Stem Cell Rev. Rep.202016597999110.1007/s12015‑020‑10015‑832740891
     [Google Scholar]
  218. KaraözE. Çetinalp DemircanP. ErmanG. GüngörürlerE. Eker SarıboyacıA. Comparative analyses of immunosuppressive characteristics of bone-marrow, wharton’s jelly, and adipose tissue-derived human mesenchymal stem cells.Turk. J. Haematol.201734321322527610554
     [Google Scholar]
  219. KandulaU.R. WakeA.D. Effectiveness of RCTs pooling evidence on mesenchymal stem cell (MSC) therapeutic applications during COVID-19 epidemic: A systematic review.Biologics2023178511237223116
     [Google Scholar]
  220. RussoE. CorraoS. Di GaudioF. AlbertiG. CaprndaM. KubatkaP. KruzliakP. MiceliV. ConaldiP.G. BorlonganC.V. La RoccaG. Facing the challenges in the COVID-19 pandemic era: From standard treatments to the umbilical cord-derived mesenchymal stromal cells as a new therapeutic strategy.Cells20231212166410.3390/cells1212166437371134
     [Google Scholar]
  221. HussainM.S. SharmaG. The burden of cardiovascular diseases due to COVID-19 pandemic.Thorac. Cardiovasc. Surg.202472104005010.1055/s‑0042‑175520535987194
     [Google Scholar]
  222. GuptaG. HussainM.S. ThapaR. DahiyaR. MahapatraD.K. BhatA.A. SinglaN. SubramaniyanV. RawatS. JakhmolaV. SR. DuaK. Hope on the horizon: Wharton’s jelly mesenchymal stem cells in the fight against COVID-19.Regen. Med.202318967567810.2217/rme‑2023‑007737554111
     [Google Scholar]
  223. HeatherL.C. HafstadA.D. HaladeG.V. HarmanceyR. MellorK.M. MishraP.K. MulvihillE.E. NabbenM. NakamuraM. RiderO.J. RuizM. WendeA.R. UssherJ.R. Guidelines on models of diabetic heart disease.Am. J. Physiol. Heart Circ. Physiol.20223231H176H20010.1152/ajpheart.00058.202235657616
     [Google Scholar]
  224. HouserS.R. MarguliesK.B. MurphyA.M. SpinaleF.G. FrancisG.S. PrabhuS.D. RockmanH.A. KassD.A. MolkentinJ.D. SussmanM.A. KochW.J. American Heart Association Council on Basic Cardiovascular Sciences, Council on Clinical Cardiology, and Council on Functional Genomics and Translational Biology Animal models of heart failure: A scientific statement from the American heart association.Circ. Res.2012111113115010.1161/RES.0b013e318258252322595296
     [Google Scholar]
  225. DixonJ.A. SpinaleF.G. Large animal models of heart failure: A critical link in the translation of basic science to clinical practice.Circ. Heart Fail.20092326227110.1161/CIRCHEARTFAILURE.108.81445919808348
     [Google Scholar]
  226. MummeryC.L. DavisR.P. KriegerJ.E. Challenges in using stem cells for cardiac repair.Sci. Transl. Med.201022727ps1710.1126/scitranslmed.300055820393186
     [Google Scholar]
  227. RiehleC. BauersachsJ. Small animal models of heart failure.Cardiovasc. Res.2019115131838184910.1093/cvr/cvz16131243437
     [Google Scholar]
  228. GunataM. ParlakpinarH. Experimental heart failure models in small animals.Heart Fail. Rev.202328253355436504404
     [Google Scholar]
  229. LindseyM.L. BolliR. CantyJ.M.Jr DuX.J. FrangogiannisN.G. FrantzS. GourdieR.G. HolmesJ.W. JonesS.P. KlonerR.A. LeferD.J. LiaoR. MurphyE. PingP. PrzyklenkK. RecchiaF.A. Schwartz LongacreL. RipplingerC.M. Van EykJ.E. HeuschG. Guidelines for experimental models of myocardial ischemia and infarction.Am. J. Physiol. Heart Circ. Physiol.20183144H812H83810.1152/ajpheart.00335.201729351451
     [Google Scholar]
  230. CarllA.P. WillisM.S. LustR.M. CostaD.L. FarrajA.K. Merits of non-invasive rat models of left ventricular heart failure.Cardiovasc. Toxicol.20111129111210.1007/s12012‑011‑9103‑521279739
     [Google Scholar]
  231. SauraM. ZamoranoJ.L. ZaragozaC. Preclinical models of congestive heart failure, advantages, and limitations for application in clinical practice.Front. Physiol.20221385030110.3389/fphys.2022.85030135991184
     [Google Scholar]
  232. ShinH.S. ShinH.H. ShudoY. Current status and limitations of myocardial infarction large animal models in cardiovascular translational research.Front. Bioeng. Biotechnol.2021967368310.3389/fbioe.2021.67368333996785
     [Google Scholar]
  233. HallT.S. von LuederT.G. ZannadF. RossignolP. DuarteK. ChouihedT. DicksteinK. AtarD. AgewallS. GirerdN. High-Risk Myocardial Infarction Database Initiative investigators Relationship between left ventricular ejection fraction and mortality after myocardial infarction complicated by heart failure or left ventricular dysfunction.Int. J. Cardiol.201827226026610.1016/j.ijcard.2018.07.13730144995
     [Google Scholar]
  234. CurtisJ.P. SokolS.I. WangY. RathoreS.S. KoD.T. JadbabaieF. PortnayE.L. MarshalkoS.J. RadfordM.J. KrumholzH.M. The association of left ventricular ejection fraction, mortality, and cause of death in stable outpatients with heart failure.J. Am. Coll. Cardiol.200342473674210.1016/S0735‑1097(03)00789‑712932612
     [Google Scholar]
  235. SharpeN. DoughtyR.N. Left ventricular remodelling and improved long-term outcomes in chronic heart failure.Eur. Heart J.199819Suppl. BB36B399519350
     [Google Scholar]
  236. ClelandJ.G.F. PennellD.J. RayS.G. CoatsA.J. MacfarlaneP.W. MurrayG.D. MuleJ.D. VeredZ. LahiriA. Carvedilol hibernating reversible ischaemia trial: marker of success investigators Myocardial viability as a determinant of the ejection fraction response to carvedilol in patients with heart failure (CHRISTMAS trial): Randomised controlled trial.Lancet20033629377142110.1016/S0140‑6736(03)13801‑912853194
     [Google Scholar]
  237. WongM. StaszewskyL. LatiniR. BarleraS. GlazerR. AknayN. HesterA. AnandI. CohnJ.N. Severity of left ventricular remodeling defines outcomes and response to therapy in heart failure.J. Am. Coll. Cardiol.200443112022202710.1016/j.jacc.2003.12.05315172407
     [Google Scholar]
  238. KramerD.G. TrikalinosT.A. KentD.M. AntonopoulosG.V. KonstamM.A. UdelsonJ.E. Quantitative evaluation of drug or device effects on ventricular remodeling as predictors of therapeutic effects on mortality in patients with heart failure and reduced ejection fraction: A meta-analytic approach.J. Am. Coll. Cardiol.201056539240610.1016/j.jacc.2010.05.01120650361
     [Google Scholar]
  239. DeVoreA.D. HellkampA.S. ThomasL. AlbertN.M. ButlerJ. PattersonJ.H. SpertusJ.A. WilliamsF.B. ShenX. HernandezA.F. FonarowG.C. The association of improvement in left ventricular ejection fraction with outcomes in patients with heart failure with reduced ejection fraction: Data from CHAMP‐HF.Eur. J. Heart Fail.202224576277010.1002/ejhf.248635293088
     [Google Scholar]
  240. PensaA.V. KhanS.S. ShahR.V. WilcoxJ.E. Heart failure with improved ejection fraction: Beyond diagnosis to trajectory analysis.Prog. Cardiovasc. Dis.20248210211210.1016/j.pcad.2024.01.01438244827
     [Google Scholar]
  241. LatifpourM. Nematollahi-MahaniS.N. DeilamyM. AzimzadehB.S. Eftekhar-VaghefiS.H. NabipourF. NajafipourH. NakhaeeN. YaghoubiM. Eftekhar-VaghefiR. SalehinejadP. AziziH. Improvement in cardiac function following transplantation of human umbilical cord matrix-derived mesenchymal cells.Cardiology2011120191810.1159/00033258122085866
     [Google Scholar]
  242. WuQ. ChenB. LiangZ. Mesenchymal stem cells as a prospective therapy for the diabetic foot.Stem Cells Int.201620161461216710.1155/2016/461216727867398
     [Google Scholar]
  243. KwiatkowskiT. Zbierska-RubinkiewiczK. KrzywonJ. MajkaM. JarochaD. KijowskiJ. BrzychczyA. MusialekP. TrystulaM. Combined intra-arterial and intra-muscular transfer of Wharton’s jelly mesenchymal stem/stromal cells in no-option critical limb ischemia – The CIRCULATE N-O CLI Pilot Study.Postepy Kardiol. Interwencyjnej202218443944510.5114/aic.2022.12096336967850
     [Google Scholar]
  244. DrabikL. MazurekA. CzyżŁ. TekieliŁ. SzotW. KwiecieńE. BanyśR.P. Urbańczyk-ZawadzkaM. BorkowskaE. KozynackaA. SkuberaM. Brzyszczyk-MarzecM. KostkiewiczM. MajkaM. PodolecP. MusiałekP. Multi-modality imaging in the CIRCULATE-AMI pilot study cohort: A framework for an imaging-based randomized controlled trial of Wharton jelly mesenchymal stem cell use to stimulate myocardial repair/regeneration.Postepy Kardiol. Interwencyjnej202218449649910.5114/aic.2023.12436136967846
     [Google Scholar]
  245. MusialekP. TekieliL. KostkiewiczM. MajkaM. SzotW. WalterZ. ZebzdaA. PieniazekP. KadzielskiA. BanysR.P. OlszowskaM. PasowiczM. ZmudkaK. TraczW. Randomized transcoronary delivery of CD34+ cells with perfusion versus stop-flow method in patients with recent myocardial infarction: Early cardiac retention of 99mTc-labeled cells activity.J. Nucl. Cardiol.201118110411610.1007/s12350‑010‑9326‑z21161463
     [Google Scholar]
  246. Sampaio-PintoV SilvaAC Cardiac regeneration and repair: From mechanisms to therapeutic strategies.In: Learning Materials in BiosciencesSpringerCham202018721110.1007/978‑3‑030‑43939‑2_10
     [Google Scholar]
  247. SepantafarM. MaheronnaghshR. MohammadiH. Rajabi-ZeletiS. AnnabiN. AghdamiN. BaharvandH. Stem cells and injectable hydrogels: Synergistic therapeutics in myocardial repair.Biotechnol. Adv.201634436237910.1016/j.biotechadv.2016.03.00326976812
     [Google Scholar]
  248. GaoB. MatsuuraK. ShimizuT. Recent progress in induced pluripotent stem cell-derived cardiac cell sheets for tissue engineering.Biosci. Trends201913429229810.5582/bst.2019.0122731527326
     [Google Scholar]
  249. MancusoA. BaroneA. CristianoM.C. CianfloneE. FrestaM. PaolinoD. Cardiac stem cell-loaded delivery systems: A new challenge for myocardial tissue regeneration.Int. J. Mol. Sci.20202120770110.3390/ijms2120770133080988
     [Google Scholar]
  250. HeX. WangQ. ZhaoY. ZhangH. WangB. PanJ. LiJ. YuH. WangL. DaiJ. WangD. Effect of intramyocardial grafting collagen scaffold with mesenchymal stromal cells in patients with chronic ischemic heart disease.JAMA Netw. Open202039e201623610.1001/jamanetworkopen.2020.1623632910197
     [Google Scholar]
  251. TadevosyanK. Iglesias-GarcíaO. MazoM.M. PrósperF. RayaA. Engineering and assessing cardiac tissue complexity.Int. J. Mol. Sci.2021223147910.3390/ijms2203147933540699
     [Google Scholar]
  252. SpiliasN. HowardT.M. AnthonyC.M. LaczayB. SolteszE.G. StarlingR.C. SievertH. EstepJ.D. KapadiaS.R. PuriR. Transcatheter left ventriculoplasty.EuroIntervention202318171399140710.4244/EIJ‑D‑22‑0054437092265
     [Google Scholar]
  253. BilirgenA.C. TokerM. OdabasS. YetisenA.K. GaripcanB. TasogluS. Plant-based scaffolds in tissue engineering.ACS Biomater. Sci. Eng.20217392693810.1021/acsbiomaterials.0c0152733591719
     [Google Scholar]
  254. ZhengY. WangW. CaiP. ZhengF. ZhouY. LiM. DuJ. LinS. LinH. Stem cell-derived exosomes in the treatment of acute myocardial infarction in preclinical animal models: A meta-analysis of randomized controlled trials.Stem Cell Res. Ther.202213115110.1186/s13287‑022‑02833‑z35395872
     [Google Scholar]
  255. GomeG. ChakB. TawilS. ShpatzD. GironJ. BrajzblatI. WeizmanC. GrishkoA. SchlesingerS. ShoseyovO. Cultivation of bovine mesenchymal stem cells on plant-based scaffolds in a macrofluidic single-use bioreactor for cultured meat.Foods2024139136110.3390/foods1309136138731732
     [Google Scholar]
  256. HussainM.S. AltamimiA.S.A. AfzalM. AlmalkiW.H. KazmiI. AlzareaS.I. GuptaG. ShahwanM. KukretiN. WongL.S. KumarasamyV. SubramaniyanV. Kaempferol: Paving the path for advanced treatments in aging-related diseases.Exp. Gerontol.202418811238910.1016/j.exger.2024.11238938432575
     [Google Scholar]
  257. KishinoY. FukudaK. Unlocking the pragmatic potential of regenerative therapies in heart failure with next-generation treatments.Biomedicines202311391510.3390/biomedicines1103091536979894
     [Google Scholar]
  258. KwiecienE. DrabikL. MazurekA. JarochaD. UrbanczykM. SzotW. BanysR. Kozynacka-FrasA. PlazakW. OlszowskaM. SobczykD. KostkiewiczM. MajkaM. PodolecP. MusialekP. Acute myocardial infarction reparation/regeneration strategy using Wharton’s jelly multipotent stem cells as an ‘unlimited’ therapeutic agent: 3-year outcomes in a pilot cohort of the CIRCULATE-AMI trial.Postepy Kardiol. Interwencyjnej202218447648210.5114/aic.2022.12112536967843
     [Google Scholar]
  259. KavousiS. HosseinpourA. Bahmanzadegan JahromiF. AttarA. Efficacy of mesenchymal stem cell transplantation on major adverse cardiovascular events and cardiac function indices in patients with chronic heart failure: A meta-analysis of randomized controlled trials.J. Transl. Med.202422178610.1186/s12967‑024‑05352‑y39174960
     [Google Scholar]
  260. BilewskaA. AbdullahM. MishraR. MusialekP. GunasekaranM. SahaP. StefanowiczA. MehtaV. SharmaS. KaushalS. Safety and efficacy of transcoronary transfer of human neonatal stem cells to ischemic myocardium using a novel cell-delivery system (CIRCULATE catheter) in swine model of acute myocardial infarction.Postepy Kardiol. Interwencyjnej202218443143810.5114/aic.2022.12169736967844
     [Google Scholar]
/content/journals/ccr/10.2174/011573403X372908250117092252
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Umbilical Cord Matrix (Wharton Jelly) Mesenchymal Stem Cells in Next-generation Myocardial Repair and Regeneration: Mechanisms and Pre-clinical Evidence
Curr. Cardiol. Rev. 21, E1573403X372908 (2025); https://doi.org/10.2174/011573403X372908250117092252
/content/journals/ccr/10.2174/011573403X372908250117092252
/content/journals/ccr/10.2174/011573403X372908250117092252
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  • Article Type:     Review Article
Keyword(s): acute myocardial infarction (AMI); advanced therapy medicinal product (ATMP); animal models of human disease; chronic ischemic heart failure (CIHF); myocardial regeneration; myocardial repair; stem cells; umbilical cord; Wharton’s Jelly mesenchymal stem cells (WJMSCs)

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