Bridging the Translational Gap in Heart Failure Research: Using Human iPSC-derived Cardiomyocytes to Accelerate Therapeutic Insights

Leslye Venegas-Zamora; Matthew Fiedler; William Perez; Francisco Altamirano

doi:10.14797/mdcvj.1295

Bridging the Translational Gap in Heart Failure Research: Using Human iPSC-derived Cardiomyocytes to Accelerate Therapeutic Insights

Methodist DeBakey Cardiovascular Journal

Volume 19 (2023): Issue 5

By: Leslye Venegas-Zamora , Matthew Fiedler , William Perez and Francisco Altamirano

Open Access

|Nov 2023

Benjamin EJ, Blaha MJ, Chiuve SE, et al. Heart Disease and Stroke Statistics-2017 Update: A Report From the American Heart Association. Circulation. 2017 Mar 7;135(10):e146–e603. Epub 20170125. doi: 10.1161/CIR.0000000000000485
Open DOI Search in Google Scholar Back to article
Heidenreich PA, Bozkurt B, Aguilar D, et al. 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2022 May 3;145(18):e895–e1032. doi: 10.1161/CIR.0000000000001063
Open DOI Search in Google Scholar Back to article
Noll NA, Lal H, Merryman WD. Mouse Models of Heart Failure with Preserved or Reduced Ejection Fraction. Am J Pathol. 2020 Aug;190(8):1596–608. Epub 20200425. doi: 10.1016/j.ajpath.2020.04.006
Open DOI Search in Google Scholar Back to article
Roh J, Hill JA, Singh A, Valero-Munoz M, Sam F. Heart Failure With Preserved Ejection Fraction: Heterogeneous Syndrome, Diverse Preclinical Models. Circ Res. 2022 Jun 10;130(12):1906–25. doi: 10.1161/CIRCRESAHA.122.320257
Open DOI Search in Google Scholar Back to article
Gao E, Koch WJ. A novel and efficient model of coronary artery ligation in the mouse. Methods Mol Biol. 2013;1037:299–311. doi: 10.1007/978-1-62703-505-7_17
Open DOI Search in Google Scholar Back to article
Kim SC, Boehm O, Meyer R, Hoeft A, Knufermann P, Baumgarten G. A murine closed-chest model of myocardial ischemia and reperfusion. J Vis Exp. 2012 Jul 17;(65):e3896. Epub 20120717. doi: 10.3791/3896
Open DOI Search in Google Scholar Back to article
Belhomme D, Peynet J, Louzy M, Launay JM, Kitakaze M, Menasche P. Evidence for preconditioning by isoflurane in coronary artery bypass graft surgery. Circulation. 1999 Nov 9;100(19 Suppl):II340–4. doi: 10.1161/01.cir.100.suppl_2.ii-340
Open DOI Search in Google Scholar Back to article
Riess ML, Stowe DF, Warltier DC. Cardiac pharmacological preconditioning with volatile anesthetics: from bench to bedside? Am J Physiol Heart Circ Physiol. 2004 May;286(5):H1603–7. doi: 10.1152/ajpheart.00963.2003
Open DOI Search in Google Scholar Back to article
Andersson KB, Birkeland JA, Finsen AV, et al. Moderate heart dysfunction in mice with inducible cardiomyocyte-specific excision of the Serca2 gene. J Mol Cell Cardiol. 2009 Aug;47(2):180–7. doi: 10.1016/j.yjmcc.2009.03.013
Open DOI Search in Google Scholar Back to article
Schultz Jel J, Glascock BJ, Witt SA, et al. Accelerated onset of heart failure in mice during pressure overload with chronically decreased SERCA2 calcium pump activity. Am J Physiol Heart Circ Physiol. 2004 Mar;286(3):H1146–53. doi: 10.1152/ajpheart.00720.2003
Open DOI Search in Google Scholar Back to article
Greenberg B, Butler J, Felker GM, et al. Calcium upregulation by percutaneous administration of gene therapy in patients with cardiac disease (CUPID 2): a randomised, multinational, double-blind, placebo-controlled, phase 2b trial. Lancet. 2016 Mar 19;387(10024):1178–86. doi: 10.1016/S0140-6736(16)00082-9
Open DOI Search in Google Scholar Back to article
Hulot JS, Salem JE, Redheuil A, et al. Effect of intracoronary administration of AAV1/SERCA2a on ventricular remodelling in patients with advanced systolic heart failure: results from the AGENT-HF randomized phase 2 trial. Eur J Heart Fail. 2017 Nov;19(11):1534–41. doi: 10.1002/ejhf.826
Open DOI Search in Google Scholar Back to article
Lyon AR, Babalis D, Morley-Smith AC, et al. Investigation of the safety and feasibility of AAV1/SERCA2a gene transfer in patients with chronic heart failure supported with a left ventricular assist device - the SERCA-LVAD TRIAL. Gene Ther. 2020 Dec;27(12):579–90. doi: 10.1038/s41434-020-0171-7
Open DOI Search in Google Scholar Back to article
Ragone I, Barallobre-Barreiro J, Takov K, et al. SERCA2a Protein Levels Are Unaltered in Human Heart Failure. Circulation. 2023 Aug 15;148(7):613–6. doi: 10.1161/CIRCULATIONAHA.123.064513
Open DOI Search in Google Scholar Back to article
Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell. 2006 Aug 25;126(4):663–76. doi: 10.1016/j.cell.2006.07.024
Open DOI Search in Google Scholar Back to article
Burridge PW, Matsa E, Shukla P, et al. Chemically defined generation of human cardiomyocytes. Nat Methods. 2014 Aug;11(8):855–60. doi: 10.1038/nmeth.2999
Open DOI Search in Google Scholar Back to article
Pilz PM, Ward JE, Chang WT, et al. Large and Small Animal Models of Heart Failure With Reduced Ejection Fraction. Circ Res. 2022 Jun 10;130(12):1888–905. doi: 10.1161/CIRCRESAHA.122.320246
Open DOI Search in Google Scholar Back to article
Silva KAS, Emter CA. Large Animal Models of Heart Failure: A Translational Bridge to Clinical Success. JACC Basic Transl Sci. 2020 Aug 24;5(8):840–56. doi: 10.1016/j.jacbts.2020.04.011
Open DOI Search in Google Scholar Back to article
Riehle C, Bauersachs J. Small animal models of heart failure. Cardiovasc Res. 2019 Nov 1;115(13):1838–49. doi: 10.1093/cvr/cvz161
Open DOI Search in Google Scholar Back to article
Lindsey ML, Brunt KR, Kirk JA, et al. Guidelines for in vivo mouse models of myocardial infarction. Am J Physiol Heart Circ Physiol. 2021 Dec 1;321(6):H1056–H73. doi: 10.1152/ajpheart.00459.2021
Open DOI Search in Google Scholar Back to article
Park S, Ranjbarvaziri S, Lay FD, et al. Genetic Regulation of Fibroblast Activation and Proliferation in Cardiac Fibrosis. Circulation. 2018 Sep 18;138(12):1224–35. doi: 10.1161/CIRCULATIONAHA.118.035420
Open DOI Search in Google Scholar Back to article
Batkai S, Genschel C, Viereck J, et al. CDR132L improves systolic and diastolic function in a large animal model of chronic heart failure. Eur Heart J. 2021 Jan 7;42(2):192–201. doi: 10.1093/eurheartj/ehaa791
Open DOI Search in Google Scholar Back to article
Bikou O, Watanabe S, Hajjar RJ, Ishikawa K. A Pig Model of Myocardial Infarction: Catheter-Based Approaches. Methods Mol Biol. 2018;1816:281–94. doi: 10.1007/978-1-4939-8597-5_22
Open DOI Search in Google Scholar Back to article
Franciosa JA, Heckel R, Limas C, Cohn JN. Progressive myocardial dysfunction associated with increased vascular resistance. Am J Physiol. 1980 Oct;239(4):H477–H82. doi: 10.1152/ajpheart.1980.239.4.H477
Open DOI Search in Google Scholar Back to article
Sun S, Jiang Y, Zhen Z, Lai WH, Liao S, Tse HF. Establishing a Swine Model of Post-myocardial Infarction Heart Failure for Stem Cell Treatment. J Vis Exp. 2020 May 25(159). doi: 10.3791/60392
Open DOI Search in Google Scholar Back to article
Lubberding AF, Sattler SM, Flethoj M, Tfelt-Hansen J, Jespersen T. Comparison of hemodynamics, cardiac electrophysiology, and ventricular arrhythmia in an open- and a closed-chest porcine model of acute myocardial infarction. Am J Physiol Heart Circ Physiol. 2020 Feb 1;318(2):H391–H400. doi: 10.1152/ajpheart.00406.2019
Open DOI Search in Google Scholar Back to article
Claycomb WC, Lanson, NA Jr, Stallworth BS, et al. HL-1 cells: a cardiac muscle cell line that contracts and retains phenotypic characteristics of the adult cardiomyocyte. Proc Natl Acad Sci U S A. 1998 Mar 17;95(6):2979–84. doi: 10.1073/pnas.95.6.2979
Open DOI Search in Google Scholar Back to article
Hescheler J, Meyer R, Plant S, Krautwurst D, Rosenthal W, Schultz G. Morphological, biochemical, and electrophysiological characterization of a clonal cell (H9c2) line from rat heart. Circ Res. 1991 Dec;69(6):1476–86. doi: 10.1161/01.res.69.6.1476
Open DOI Search in Google Scholar Back to article
Kimes BW, Brandt BL. Properties of a clonal muscle cell line from rat heart. Exp Cell Res. 1976 Mar 15;98(2):367–81. doi: 10.1016/0014-4827(76)90447-x
Open DOI Search in Google Scholar Back to article
Davidson MM, Nesti C, Palenzuela L, et al. Novel cell lines derived from adult human ventricular cardiomyocytes. J Mol Cell Cardiol. 2005 Jul;39(1):133–47. doi: 10.1016/j.yjmcc.2005.03.003
Open DOI Search in Google Scholar Back to article
Onodi Z, Visnovitz T, Kiss B, et al. Systematic transcriptomic and phenotypic characterization of human and murine cardiac myocyte cell lines and primary cardiomyocytes reveals serious limitations and low resemblances to adult cardiac phenotype. J Mol Cell Cardiol. 2022 Apr;165:19–30. doi: 10.1016/j.yjmcc.2021.12.007
Open DOI Search in Google Scholar Back to article
Champattanachai V, Marchase RB, Chatham JC. Glucosamine protects neonatal cardiomyocytes from ischemia-reperfusion injury via increased protein O-GlcNAc and increased mitochondrial Bcl-2. Am J Physiol Cell Physiol. 2008;294(6):C1509–20. doi: 10.1152/ajpcell.00456.2007
Open DOI Search in Google Scholar Back to article
de Diego C, Pai RK, Chen F, et al. Electrophysiological consequences of acute regional ischemia/reperfusion in neonatal rat ventricular myocyte monolayers. Circulation. 2008 Dec 2;118(23):2330–7. doi: 10.1161/CIRCULATIONAHA.108.789149
Open DOI Search in Google Scholar Back to article
Lin J, Li Q, Jin T, et al. Cardiomyocyte IL-1R2 protects heart from ischemia/reperfusion injury by attenuating IL-17RA-mediated cardiomyocyte apoptosis. Cell Death Dis. 2022;13(1):90. doi: 10.1038/s41419-022-04533-1
Open DOI Search in Google Scholar Back to article
Pitoulis FG, Watson SA, Perbellini F, Terracciano CM. Myocardial slices come to age: an intermediate complexity in vitro cardiac model for translational research. Cardiovasc Res. 2020 Jun 1;116(7):1275–87. doi: 10.1093/cvr/cvz341
Open DOI Search in Google Scholar Back to article
Xu C, Police S, Rao N, Carpenter MK. Characterization and enrichment of cardiomyocytes derived from human embryonic stem cells. Circ Res. 2002;91(6):501–8. doi: 10.1161/01.res.0000035254.80718.91
Open DOI Search in Google Scholar Back to article
Zhang J, Wilson GF, Soerens AG, et al. Functional cardiomyocytes derived from human induced pluripotent stem cells. Circ Res. 2009;104(4):e30–41. doi: 10.1161/CIRCRESAHA
Open DOI Search in Google Scholar Back to article
Lian X, Hsiao C, Wilson G, et al. Robust cardiomyocyte differentiation from human pluripotent stem cells via temporal modulation of canonical Wnt signaling. Proc Natl Acad Sci U S A. 2012;109(27):E1848–57. doi: 10.1073/pnas.1200250109
Open DOI Search in Google Scholar Back to article
Buikema JW, Lee S, Goodyer WR, et al. Wnt Activation and Reduced Cell-Cell Contact Synergistically Induce Massive Expansion of Functional Human iPSC-Derived Cardiomyocytes. Cell Stem Cell. 2020;27(1):50–63 e5. doi: 10.1016/j.stem.2020.06.001
Open DOI Search in Google Scholar Back to article
Maas RGC, Lee S, Harakalova M, et al. Massive expansion and cryopreservation of functional human induced pluripotent stem cell-derived cardiomyocytes. STAR Protoc. 2021 Feb 9;2(1):100334. doi: 10.1016/j.xpro.2021.100334
Open DOI Search in Google Scholar Back to article
Hill JA, Olson EN. Cardiac plasticity. N Engl J Med. 2008 Mar 27;358(13):1370–80. doi: 10.1056/NEJMra072139
Open DOI Search in Google Scholar Back to article
Cho GW, Altamirano F, Hill JA. Chronic heart failure: Ca(2+), catabolism, and catastrophic cell death. Biochim Biophys Acta. 2016;1862(4):763–77. doi: 10.1016/j.bbadis.2016.01.011
Open DOI Search in Google Scholar Back to article
Altamirano F, Wang ZV, Hill JA. Cardioprotection in ischaemia-reperfusion injury: novel mechanisms and clinical translation. J Physiol. 2015 Sep 1;593(17):3773–88. doi: 10.1113/JP270953
Open DOI Search in Google Scholar Back to article
Peters MC, Maas RGC, van Adrichem I, et al. Metabolic Maturation Increases Susceptibility to Hypoxia-induced Damage in Human iPSC-derived Cardiomyocytes. Stem Cells Transl Med. 2022;11(10):1040–51. doi: 10.1093/stcltm/szac061
Open DOI Search in Google Scholar Back to article
Hidalgo A, Glass N, Ovchinnikov D, et al. Modelling ischemia-reperfusion injury (IRI) in vitro using metabolically matured induced pluripotent stem cell-derived cardiomyocytes. APL Bioeng. 2018;2(2):026102. doi: 10.1063/1.5000746
Open DOI Search in Google Scholar Back to article
Pohjolainen L, Ruskoaho H, Talman V. Transcriptomics reveal stretched human pluripotent stem cell-derived cardiomyocytes as an advantageous hypertrophy model. JMCC Plus. 2022 Dec;2:1–14. doi: 10.1016/j.jmccpl.2022.100020
Open DOI Search in Google Scholar Back to article
Ovchinnikova E, Hoes M, Ustyantsev K, et al. Modeling Human Cardiac Hypertrophy in Stem Cell-Derived Cardiomyocytes. Stem Cell Reports. 2018;10(3):794–807. doi: 10.1016/j.stemcr.2018.01.016
Open DOI Search in Google Scholar Back to article
Johansson M, Ulfenborg B, Andersson CX, et al. Cardiac hypertrophy in a dish: a human stem cell based model. Biol Open. 2020;9(9). doi: 10.1242/bio.052381
Open DOI Search in Google Scholar Back to article
Vigil-Garcia M, Demkes CJ, Eding JEC, et al. Gene expression profiling of hypertrophic cardiomyocytes identifies new players in pathological remodelling. Cardiovasc Res. 2021;117(6):1532–45. doi: 10.1093/cvr/cvaa233
Open DOI Search in Google Scholar Back to article
Karbassi E, Fenix A, Marchiano S, et al. Cardiomyocyte maturation: advances in knowledge and implications for regenerative medicine. Nat Rev Cardiol. 2020;17(6):341–59. doi: 10.1038/s41569-019-0331-x
Open DOI Search in Google Scholar Back to article
Thomas D, Cunningham NJ, Shenoy S, Wu JC. Human-induced pluripotent stem cells in cardiovascular research: current approaches in cardiac differentiation, maturation strategies, and scalable production. Cardiovasc Res. 2022;118(1):20–36. doi: 10.1093/cvr/cvab115
Open DOI Search in Google Scholar Back to article
Feaster TK, Cadar AG, Wang L, et al. Matrigel Mattress: A Method for the Generation of Single Contracting Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes. Circ Res. 2015;117(12):995–1000. doi: 10.1161/CIRCRESAHA.115.307580
Open DOI Search in Google Scholar Back to article
Strimaityte D, Tu C, Yanez A, et al. Contractility and Calcium Transient Maturation in the Human iPSC-Derived Cardiac Microfibers. ACS Appl Mater Interfaces. 2022;14(31):35376–88. doi: 10.1021/acsami.2c07326
Open DOI Search in Google Scholar Back to article
Parikh SS, Blackwell DJ, Gomez-Hurtado N, et al. Thyroid and Glucocorticoid Hormones Promote Functional T-Tubule Development in Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes. Circ Res. 2017;121(12):1323–30. doi: 10.1161/CIRCRESAHA.117.311920
Open DOI Search in Google Scholar Back to article
Yang X, Rodriguez M, Pabon L, et al. Tri-iodo-l-thyronine promotes the maturation of human cardiomyocytes-derived from induced pluripotent stem cells. J Mol Cell Cardiol. 2014;72:296–304. doi: 10.1016/j.yjmcc.2014.04.005
Open DOI Search in Google Scholar Back to article
Funakoshi S, Fernandes I, Mastikhina O, et al. Generation of mature compact ventricular cardiomyocytes from human pluripotent stem cells. Nat Commun. 2021;12(1):3155. doi: 10.1038/s41467-021-23329-z
Open DOI Search in Google Scholar Back to article
Yang X, Rodriguez ML, Leonard A, et al. Fatty Acids Enhance the Maturation of Cardiomyocytes Derived from Human Pluripotent Stem Cells. Stem Cell Reports. 2019;13(4):657–68. doi: 10.1016/j.stemcr.2019.08.013
Open DOI Search in Google Scholar Back to article
Ronaldson-Bouchard K, Ma SP, Yeager K, et al. Advanced maturation of human cardiac tissue grown from pluripotent stem cells. Nature. 2018;556(7700):239–43. doi: 10.1038/s41586-018-0016-3
Open DOI Search in Google Scholar Back to article
Huang CY, Peres Moreno Maia-Joca R, Ong CS, et al. Enhancement of human iPSC-derived cardiomyocyte maturation by chemical conditioning in a 3D environment. J Mol Cell Cardiol. 2020;138:1–11. doi: 10.1016/j.yjmcc.2019.10.001
Open DOI Search in Google Scholar Back to article
Hansen A, Eder A, Bonstrup M, et al. Development of a drug screening platform based on engineered heart tissue. Circ Res. 2010;107(1):35–44. doi: 10.1161/CIRCRESAHA.109.211458
Open DOI Search in Google Scholar Back to article
Little RC, Little WC. Cardiac preload, afterload, and heart failure. Arch Intern Med. 1982;142(4):819–22. PMID: 7073422
Search in Google Scholar Back to article
Tamargo MA, Nash TR, Fleischer S, et al. milliPillar: A Platform for the Generation and Real-Time Assessment of Human Engineered Cardiac Tissues. ACS Biomater Sci Eng. 2021;7(11):5215–29. doi: 10.1021/acsbiomaterials.1c01006
Open DOI Search in Google Scholar Back to article
Beauchamp P, Jackson CB, Ozhathil LC, et al. 3D Co-culture of hiPSC-Derived Cardiomyocytes With Cardiac Fibroblasts Improves Tissue-Like Features of Cardiac Spheroids. Front Mol Biosci. 2020;7:14. doi: 10.3389/fmolb.2020.00014
Open DOI Search in Google Scholar Back to article
Kahn-Krell A, Pretorius D, Guragain B, et al. A three-dimensional culture system for generating cardiac spheroids composed of cardiomyocytes, endothelial cells, smooth-muscle cells, and cardiac fibroblasts derived from human induced-pluripotent stem cells. Front Bioeng Biotechnol. 2022;10:908848. doi: 10.3389/fbioe.2022.908848
Open DOI Search in Google Scholar Back to article
Coyle R, Yao J, Richards D, Mei Y. The Effects of Metabolic Substrate Availability on Human Adipose-Derived Stem Cell Spheroid Survival. Tissue Eng Part A. 2019;25(7–8):620–31. doi: 10.1089/ten.TEA.2018.0163
Open DOI Search in Google Scholar Back to article
Beauchamp P, Moritz W, Kelm JM, et al. Development and Characterization of a Scaffold-Free 3D Spheroid Model of Induced Pluripotent Stem Cell-Derived Human Cardiomyocytes. Tissue Eng Part C Methods. 2015;21(8):852–61. doi: 10.1089/ten.TEC.2014.0376
Open DOI Search in Google Scholar Back to article
Figtree GA, Bubb KJ, Tang O, Kizana E, Gentile C. Vascularized Cardiac Spheroids as Novel 3D in vitro Models to Study Cardiac Fibrosis. Cells Tissues Organs. 2017;204(3–4):191–8. doi: 10.1159/000477436
Open DOI Search in Google Scholar Back to article
Sharma P, Beck D, Murtha LA, Figtree G, Boyle A, Gentile C. Fibulin-3 Deficiency Protects Against Myocardial Injury Following Ischaemia/ Reperfusion in in vitro Cardiac Spheroids. Front Cardiovasc Med. 2022;9:913156. doi: 10.3389/fcvm.2022.913156
Open DOI Search in Google Scholar Back to article
Mukae Y, Itoh M, Noguchi R, et al. The addition of human iPS cell-derived neural progenitors changes the contraction of human iPS cell-derived cardiac spheroids. Tissue Cell. 2018;53:61–7. doi: 10.1016/j.tice.2018.05.002
Open DOI Search in Google Scholar Back to article
Torisawa YS, Mosadegh B, Luker GD, Morell M, O’Shea KS, Takayama S. Microfluidic hydrodynamic cellular patterning for systematic formation of co-culture spheroids. Integr Biol (Camb). 2009;1(11–12):649–54. doi: 10.1039/b915965g
Open DOI Search in Google Scholar Back to article
Desroches BR, Zhang P, Choi BR, et al. Functional scaffold-free 3-D cardiac microtissues: a novel model for the investigation of heart cells. Am J Physiol Heart Circ Physiol. 2012;302(10):H2031–42. doi: 10.1152/ajpheart.00743.2011
Open DOI Search in Google Scholar Back to article
Voges HK, Mills RJ, Elliott DA, Parton RG, Porrello ER, Hudson JE. Development of a human cardiac organoid injury model reveals innate regenerative potential. Development. 2017;144(6):1118–27. doi: 10.1242/dev.143966
Open DOI Search in Google Scholar Back to article
Hofbauer P, Jahnel SM, Papai N, et al. Cardioids reveal self-organizing principles of human cardiogenesis. Cell. 2021;184(12):3299–317 e22. doi: 10.1016/j.cell.2021.04.034
Open DOI Search in Google Scholar Back to article
Chen T, Vunjak-Novakovic G. Human Tissue-Engineered Model of Myocardial Ischemia-Reperfusion Injury. Tissue Eng Part A. 2019;25(9–10):711–24. doi: 10.1089/ten.TEA.2018.0212
Open DOI Search in Google Scholar Back to article
Richards DJ, Li Y, Kerr CM, et al. Human cardiac organoids for the modelling of myocardial infarction and drug cardiotoxicity. Nat Biomed Eng. 2020;4(4):446–62. doi: 10.1038/s41551-020-0539-4
Open DOI Search in Google Scholar Back to article
Acun A, Nguyen TD, Zorlutuna P. In vitro aged, hiPSC-origin engineered heart tissue models with age-dependent functional deterioration to study myocardial infarction. Acta Biomater. 2019;94:372–91. doi: 10.1016/j.actbio.2019.05.064
Open DOI Search in Google Scholar Back to article

Authors

Metrics

Articles in this issue

DOI: https://doi.org/10.14797/mdcvj.1295 | Journal eISSN: 1947-6108

Journal RSS Feed

Language: English

Page range: 5 - 15

Submitted on: Sep 18, 2023

Accepted on: Oct 4, 2023

Published on: Nov 16, 2023

Published by: Houston Methodist DeBakey Heart & Vascular Center

In partnership with: Paradigm Publishing Services

Keywords:

heart failure,

cardiomyocytes,

hypoxia,

ischemia and reperfusion injury,

stem cells

© 2023 Leslye Venegas-Zamora, Matthew Fiedler, William Perez, Francisco Altamirano, published by Houston Methodist DeBakey Heart & Vascular Center
This work is licensed under the Creative Commons Attribution-NonCommercial 4.0 License.

Volume 19 (2023): Issue 5