Advances in 3D Organoid Models for Stem Cell-Based Cardiac Regeneration

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2023 Mar 29

PMID 36982261

Authors

Marcy Martin

Eric K N Gahwiler

Melanie Generali

Simon P Hoerstrup

Maximilian Y Emmert

Affiliations

Soon will be listed here.

Abstract

The adult human heart cannot regain complete cardiac function following tissue injury, making cardiac regeneration a current clinical unmet need. There are a number of clinical procedures aimed at reducing ischemic damage following injury; however, it has not yet been possible to stimulate adult cardiomyocytes to recover and proliferate. The emergence of pluripotent stem cell technologies and 3D culture systems has revolutionized the field. Specifically, 3D culture systems have enhanced precision medicine through obtaining a more accurate human microenvironmental condition to model disease and/or drug interactions in vitro. In this study, we cover current advances and limitations in stem cell-based cardiac regenerative medicine. Specifically, we discuss the clinical implementation and limitations of stem cell-based technologies and ongoing clinical trials. We then address the advent of 3D culture systems to produce cardiac organoids that may better represent the human heart microenvironment for disease modeling and genetic screening. Finally, we delve into the insights gained from cardiac organoids in relation to cardiac regeneration and further discuss the implications for clinical translation.

Citing Articles

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References

Zamani M, Karaca E, Huang N . Multicellular Interactions in 3D Engineered Myocardial Tissue. Front Cardiovasc Med. 2018; 5:147. PMC: 6205951. DOI: 10.3389/fcvm.2018.00147. View

Hofbauer P, Jahnel S, Papai N, Giesshammer M, Deyett A, Schmidt C . Cardioids reveal self-organizing principles of human cardiogenesis. Cell. 2021; 184(12):3299-3317.e22. DOI: 10.1016/j.cell.2021.04.034. View

Tenreiro M, Louro A, Alves P, Serra M . Next generation of heart regenerative therapies: progress and promise of cardiac tissue engineering. NPJ Regen Med. 2021; 6(1):30. PMC: 8169890. DOI: 10.1038/s41536-021-00140-4. View

Murakami M, Simons M . Fibroblast growth factor regulation of neovascularization. Curr Opin Hematol. 2008; 15(3):215-20. PMC: 2745288. DOI: 10.1097/MOH.0b013e3282f97d98. View

Ishida M, Miyagawa S, Saito A, Fukushima S, Harada A, Ito E . Transplantation of Human-induced Pluripotent Stem Cell-derived Cardiomyocytes Is Superior to Somatic Stem Cell Therapy for Restoring Cardiac Function and Oxygen Consumption in a Porcine Model of Myocardial Infarction. Transplantation. 2018; 103(2):291-298. PMC: 6365242. DOI: 10.1097/TP.0000000000002384. View

Grebenyuk S, Ranga A . Engineering Organoid Vascularization. Front Bioeng Biotechnol. 2019; 7:39. PMC: 6433749. DOI: 10.3389/fbioe.2019.00039. View

Emmert M, Wolint P, Wickboldt N, Gemayel G, Weber B, Brokopp C . Human stem cell-based three-dimensional microtissues for advanced cardiac cell therapies. Biomaterials. 2013; 34(27):6339-54. DOI: 10.1016/j.biomaterials.2013.04.034. View

Rog-Zielinska E, Norris R, Kohl P, Markwald R . The Living Scar--Cardiac Fibroblasts and the Injured Heart. Trends Mol Med. 2016; 22(2):99-114. PMC: 4737999. DOI: 10.1016/j.molmed.2015.12.006. View

Oryan A, Alidadi S, Moshiri A, Maffulli N . Bone regenerative medicine: classic options, novel strategies, and future directions. J Orthop Surg Res. 2014; 9(1):18. PMC: 3995444. DOI: 10.1186/1749-799X-9-18. View

10.

Poss K, Wilson L, Keating M . Heart regeneration in zebrafish. Science. 2002; 298(5601):2188-90. DOI: 10.1126/science.1077857. View

11.

Darehzereshki A, Rubin N, Gamba L, Kim J, Fraser J, Huang Y . Differential regenerative capacity of neonatal mouse hearts after cryoinjury. Dev Biol. 2015; 399(1):91-99. PMC: 4339535. DOI: 10.1016/j.ydbio.2014.12.018. View

12.

Yang K, Breitbart A, de Lange W, Hofsteen P, Futakuchi-Tsuchida A, Xu J . Novel Adult-Onset Systolic Cardiomyopathy Due to MYH7 E848G Mutation in Patient-Derived Induced Pluripotent Stem Cells. JACC Basic Transl Sci. 2019; 3(6):728-740. PMC: 6314962. DOI: 10.1016/j.jacbts.2018.08.008. View

13.

Voges H, Mills R, Elliott D, Parton R, Porrello E, Hudson J . Development of a human cardiac organoid injury model reveals innate regenerative potential. Development. 2017; 144(6):1118-1127. DOI: 10.1242/dev.143966. View

14.

DAmario D, Fiorini C, Campbell P, Goichberg P, Sanada F, Zheng H . Functionally competent cardiac stem cells can be isolated from endomyocardial biopsies of patients with advanced cardiomyopathies. Circ Res. 2011; 108(7):857-61. PMC: 3074470. DOI: 10.1161/CIRCRESAHA.111.241380. View

15.

Archer C, Sargeant R, Basak J, Pilling J, Barnes J, Pointon A . Characterization and Validation of a Human 3D Cardiac Microtissue for the Assessment of Changes in Cardiac Pathology. Sci Rep. 2018; 8(1):10160. PMC: 6033897. DOI: 10.1038/s41598-018-28393-y. View

16.

Zhang D, Shadrin I, Lam J, Xian H, Snodgrass H, Bursac N . Tissue-engineered cardiac patch for advanced functional maturation of human ESC-derived cardiomyocytes. Biomaterials. 2013; 34(23):5813-20. PMC: 3660435. DOI: 10.1016/j.biomaterials.2013.04.026. View

17.

Porrello E, Olson E . A neonatal blueprint for cardiac regeneration. Stem Cell Res. 2014; 13(3 Pt B):556-70. PMC: 4316722. DOI: 10.1016/j.scr.2014.06.003. View

18.

Boudou T, Legant W, Mu A, Borochin M, Thavandiran N, Radisic M . A microfabricated platform to measure and manipulate the mechanics of engineered cardiac microtissues. Tissue Eng Part A. 2011; 18(9-10):910-9. PMC: 3338105. DOI: 10.1089/ten.tea.2011.0341. View

19.

Lewis-Israeli Y, Wasserman A, Gabalski M, Volmert B, Ming Y, Ball K . Self-assembling human heart organoids for the modeling of cardiac development and congenital heart disease. Nat Commun. 2021; 12(1):5142. PMC: 8390749. DOI: 10.1038/s41467-021-25329-5. View

20.

Polonchuk L, Chabria M, Badi L, Hoflack J, Figtree G, Davies M . Cardiac spheroids as promising in vitro models to study the human heart microenvironment. Sci Rep. 2017; 7(1):7005. PMC: 5539326. DOI: 10.1038/s41598-017-06385-8. View