Maturing Human Pluripotent Stem Cell-derived Cardiomyocytes in Human Engineered Cardiac Tissues

Overview

Journal Adv Drug Deliv Rev

Specialty Pharmacology

Date 2015 May 10

PMID 25956564

Citations 114

Authors

Nicole T Feric

Milica Radisic

Affiliations

Soon will be listed here.

Abstract

Engineering functional human cardiac tissue that mimics the native adult morphological and functional phenotype has been a long held objective. In the last 5 years, the field of cardiac tissue engineering has transitioned from cardiac tissues derived from various animal species to the production of the first generation of human engineered cardiac tissues (hECTs), due to recent advances in human stem cell biology. Despite this progress, the hECTs generated to date remain immature relative to the native adult myocardium. In this review, we focus on the maturation challenge in the context of hECTs, the present state of the art, and future perspectives in terms of regenerative medicine, drug discovery, preclinical safety testing and pathophysiological studies.

Citing Articles

Integrating melt electrospinning writing and microfluidics to engineer a human cardiac microenvironment for high-fidelity drug screening.

Wang Y, Liu T, Guo Y, Zhu S, Liao Z, Song J Bioact Mater. 2025; 45:551-566.

PMID: 39759533 PMC: 11696762. DOI: 10.1016/j.bioactmat.2024.11.037.

Induced pluripotent stem cell-derived cardiomyocyte in vitro models: benchmarking progress and ongoing challenges.

Ewoldt J, DePalma S, Jewett M, Karakan M, Lin Y, Mir Hashemian P Nat Methods. 2024; 22(1):24-40.

PMID: 39516564 DOI: 10.1038/s41592-024-02480-7.

Hydrogel microsphere stem cell encapsulation enhances cardiomyocyte differentiation and functionality in scalable suspension system.

Hashemi M, Finklea F, Hammons H, Tian Y, Young N, Kim E Bioact Mater. 2024; 43:423-440.

PMID: 39399838 PMC: 11471139. DOI: 10.1016/j.bioactmat.2024.08.043.

Multidirectional Filamented Light Biofabrication Creates Aligned and Contractile Cardiac Tissues.

Jones L, Filippi M, Michelis M, Balciunaite A, Yasa O, Aviel G Adv Sci (Weinh). 2024; 11(47):e2404509.

PMID: 39373330 PMC: 11653608. DOI: 10.1002/advs.202404509.

Primitive macrophages induce sarcomeric maturation and functional enhancement of developing human cardiac microtissues via efferocytic pathways.

Hamidzada H, Pascual-Gil S, Wu Q, Kent G, Masse S, Kantores C Nat Cardiovasc Res. 2024; 3(5):567-593.

PMID: 39086373 PMC: 11290557. DOI: 10.1038/s44161-024-00471-7.

References

Carlsson L . In vitro and in vivo models for testing arrhythmogenesis in drugs. J Intern Med. 2005; 259(1):70-80. DOI: 10.1111/j.1365-2796.2005.01590.x. View

Bhana B, Iyer R, Chen W, Zhao R, Sider K, Likhitpanichkul M . Influence of substrate stiffness on the phenotype of heart cells. Biotechnol Bioeng. 2009; 105(6):1148-60. DOI: 10.1002/bit.22647. View

Cooper I, Fry C . Mechanical restitution in isolated mammalian myocardium: species differences and underlying mechanisms. J Mol Cell Cardiol. 1990; 22(4):439-52. DOI: 10.1016/0022-2828(90)91479-q. View

Silva J, Rudy Y . Mechanism of pacemaking in I(K1)-downregulated myocytes. Circ Res. 2003; 92(3):261-3. PMC: 1890031. DOI: 10.1161/01.res.0000057996.20414.c6. View

Parker T, Packer S, Schneider M . Peptide growth factors can provoke "fetal" contractile protein gene expression in rat cardiac myocytes. J Clin Invest. 1990; 85(2):507-14. PMC: 296452. DOI: 10.1172/JCI114466. View

Robertson C, Tran D, George S . Concise review: maturation phases of human pluripotent stem cell-derived cardiomyocytes. Stem Cells. 2013; 31(5):829-37. PMC: 3749929. DOI: 10.1002/stem.1331. View

Zhang S, Zhou Z, Gong Q, Makielski J, January C . Mechanism of block and identification of the verapamil binding domain to HERG potassium channels. Circ Res. 1999; 84(9):989-98. DOI: 10.1161/01.res.84.9.989. View

Mercier A, Clement R, Harnois T, Bourmeyster N, Faivre J, Findlay I . The β1-subunit of Na(v)1.5 cardiac sodium channel is required for a dominant negative effect through α-α interaction. PLoS One. 2012; 7(11):e48690. PMC: 3486797. DOI: 10.1371/journal.pone.0048690. View

FRIEDMAN W . The intrinsic physiologic properties of the developing heart. Prog Cardiovasc Dis. 1972; 15(1):87-111. DOI: 10.1016/0033-0620(72)90006-0. View

10.

Kattman S, Witty A, Gagliardi M, Dubois N, Niapour M, Hotta A . Stage-specific optimization of activin/nodal and BMP signaling promotes cardiac differentiation of mouse and human pluripotent stem cell lines. Cell Stem Cell. 2011; 8(2):228-40. DOI: 10.1016/j.stem.2010.12.008. View

11.

Ming Z, Nordin C . Terfenadine blocks time-dependent Ca2+, Na+, and K+ channels in guinea pig ventricular myocytes. J Cardiovasc Pharmacol. 1995; 26(5):761-9. DOI: 10.1097/00005344-199511000-00013. View

12.

Abell T, Richards A, Ikram H, Espiner E, Yandle T . Atrial natriuretic factor inhibits proliferation of vascular smooth muscle cells stimulated by platelet-derived growth factor. Biochem Biophys Res Commun. 1989; 160(3):1392-6. DOI: 10.1016/s0006-291x(89)80158-5. View

13.

Fu J, Li J, Tweedie D, Yu H, Chen L, Wang R . Crucial role of the sarcoplasmic reticulum in the developmental regulation of Ca2+ transients and contraction in cardiomyocytes derived from embryonic stem cells. FASEB J. 2005; 20(1):181-3. DOI: 10.1096/fj.05-4501fje. View

14.

CAIN B, Meldrum D, Meng X, Shames B, Banerjee A, Harken A . Calcium preconditioning in human myocardium. Ann Thorac Surg. 1998; 65(4):1065-70. DOI: 10.1016/s0003-4975(98)00093-9. View

15.

Cao L, Gardner D . Natriuretic peptides inhibit DNA synthesis in cardiac fibroblasts. Hypertension. 1995; 25(2):227-34. DOI: 10.1161/01.hyp.25.2.227. View

16.

Weiss S, Oz S, Benmocha A, Dascal N . Regulation of cardiac L-type Ca²⁺ channel CaV1.2 via the β-adrenergic-cAMP-protein kinase A pathway: old dogmas, advances, and new uncertainties. Circ Res. 2013; 113(5):617-31. DOI: 10.1161/CIRCRESAHA.113.301781. View

17.

Nassar R, Reedy M, Anderson P . Developmental changes in the ultrastructure and sarcomere shortening of the isolated rabbit ventricular myocyte. Circ Res. 1987; 61(3):465-83. DOI: 10.1161/01.res.61.3.465. View

18.

Grosberg A, Alford P, McCain M, Parker K . Ensembles of engineered cardiac tissues for physiological and pharmacological study: heart on a chip. Lab Chip. 2011; 11(24):4165-73. PMC: 4038963. DOI: 10.1039/c1lc20557a. View

19.

Nakanishi T, Seguchi M, TAKAO A . Development of the myocardial contractile system. Experientia. 1988; 44(11-12):936-44. DOI: 10.1007/BF01939887. View

20.

Hansen A, Eder A, Bonstrup M, Flato M, Mewe M, Schaaf S . Development of a drug screening platform based on engineered heart tissue. Circ Res. 2010; 107(1):35-44. DOI: 10.1161/CIRCRESAHA.109.211458. View