Human Induced Pluripotent Stem-Cell-Derived Cardiomyocytes As Models for Genetic Cardiomyopathies

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2019 Sep 7

PMID 31489928

Citations 33

Authors

Andreas Brodehl

Hans Ebbinghaus

Marcus-Andre Deutsch

Jan Gummert

Anna Gartner

Sandra Ratnavadivel

Hendrik Milting

Affiliations

Soon will be listed here.

Abstract

In the last few decades, many pathogenic or likely pathogenic genetic mutations in over hundred different genes have been described for non-ischemic, genetic cardiomyopathies. However, the functional knowledge about most of these mutations is still limited because the generation of adequate animal models is time-consuming and challenging. Therefore, human induced pluripotent stem cells (iPSCs) carrying specific cardiomyopathy-associated mutations are a promising alternative. Since the original discovery that pluripotency can be artificially induced by the expression of different transcription factors, various patient-specific-induced pluripotent stem cell lines have been generated to model non-ischemic, genetic cardiomyopathies in vitro. In this review, we describe the genetic landscape of non-ischemic, genetic cardiomyopathies and give an overview about different human iPSC lines, which have been developed for the disease modeling of inherited cardiomyopathies. We summarize different methods and protocols for the general differentiation of human iPSCs into cardiomyocytes. In addition, we describe methods and technologies to investigate functionally human iPSC-derived cardiomyocytes. Furthermore, we summarize novel genome editing approaches for the genetic manipulation of human iPSCs. This review provides an overview about the genetic landscape of inherited cardiomyopathies with a focus on iPSC technology, which might be of interest for clinicians and basic scientists interested in genetic cardiomyopathies.

Citing Articles

The Role of Human-Induced Pluripotent Stem Cells in Studying Cardiac Channelopathies.

Begovic M, Schneider L, Zhou X, Hamdani N, Akin I, El-Battrawy I Int J Mol Sci. 2024; 25(22).

PMID: 39596103 PMC: 11593457. DOI: 10.3390/ijms252212034.

Ferroptosis in diabetic cardiomyopathy: Advances in cardiac fibroblast-cardiomyocyte interactions.

Wang M, Mo D, Zhang N, Yu H Heliyon. 2024; 10(15):e35219.

PMID: 39165946 PMC: 11334834. DOI: 10.1016/j.heliyon.2024.e35219.

Comparison of Two Differentiation Protocols of Human-Induced Pluripotent Stem Cells into Cardiomyocytes.

Loboda A, Klaptocz M, Kazirod K, Wolnik J, Biniecka M, Stepniewski J Methods Mol Biol. 2024; 2835:69-82.

PMID: 39105907 DOI: 10.1007/978-1-0716-3995-5_7.

Patterns of Left Ventricular Remodelling in Children and Young Patients with Hypertrophic Cardiomyopathy.

Monda E, Caiazza M, Cirillo C, Rubino M, Verrillo F, Palmiero G J Clin Med. 2024; 13(13).

PMID: 38999502 PMC: 11242481. DOI: 10.3390/jcm13133937.

Case Report: Four cases of cardiac sarcoidosis in patients with inherited cardiomyopathy-a phenotypic overlap, co-existence of two rare cardiomyopathies or a second-hit disease.

Ebbinghaus H, Ueberham L, Husser-Bollmann D, Bollmann A, Laufs U, Dinov B Front Cardiovasc Med. 2024; 10:1328802.

PMID: 38173816 PMC: 10763246. DOI: 10.3389/fcvm.2023.1328802.

References

Wyles S, Hrstka S, Reyes S, Terzic A, Olson T, Nelson T . Pharmacological Modulation of Calcium Homeostasis in Familial Dilated Cardiomyopathy: An In Vitro Analysis From an RBM20 Patient-Derived iPSC Model. Clin Transl Sci. 2016; 9(3):158-67. PMC: 4902766. DOI: 10.1111/cts.12393. View

Minoche A, Horvat C, Johnson R, Gayevskiy V, Morton S, Drew A . Genome sequencing as a first-line genetic test in familial dilated cardiomyopathy. Genet Med. 2018; 21(3):650-662. PMC: 7271716. DOI: 10.1038/s41436-018-0084-7. View

Govindsamy A, Naidoo S, Cerf M . Cardiac Development and Transcription Factors: Insulin Signalling, Insulin Resistance, and Intrauterine Nutritional Programming of Cardiovascular Disease. J Nutr Metab. 2018; 2018:8547976. PMC: 5816854. DOI: 10.1155/2018/8547976. View

Khudiakov A, Kostina D, Zlotina A, Nikulina T, Sergushichev A, Gudkova A . Generation of iPSC line from desmin-related cardiomyopathy patient carrying splice site mutation of DES gene. Stem Cell Res. 2017; 24:77-80. DOI: 10.1016/j.scr.2017.08.015. View

Norton N, Li D, Rieder M, Siegfried J, Rampersaud E, Zuchner S . Genome-wide studies of copy number variation and exome sequencing identify rare variants in BAG3 as a cause of dilated cardiomyopathy. Am J Hum Genet. 2011; 88(3):273-82. PMC: 3059419. DOI: 10.1016/j.ajhg.2011.01.016. View

Meraviglia V, Benzoni P, Landi S, Murano C, Langione M, Motta B . Generation of human induced pluripotent stem cells (EURACi001-A, EURACi002-A, EURACi003-A) from peripheral blood mononuclear cells of three patients carrying mutations in the CAV3 gene. Stem Cell Res. 2018; 27:25-29. DOI: 10.1016/j.scr.2017.12.012. View

Penttinen K, Siirtola H, Avalos-Salguero J, Vainio T, Juhola M, Aalto-Setala K . Novel Analysis Software for Detecting and Classifying Ca2+ Transient Abnormalities in Stem Cell-Derived Cardiomyocytes. PLoS One. 2015; 10(8):e0135806. PMC: 4550257. DOI: 10.1371/journal.pone.0135806. View

Kiselev A, Vaz R, Knyazeva A, Khudiakov A, Tarnovskaya S, Liu J . De novo mutations in FLNC leading to early-onset restrictive cardiomyopathy and congenital myopathy. Hum Mutat. 2018; 39(9):1161-1172. DOI: 10.1002/humu.23559. View

Zhang M, Chen J, Si D, Zheng Y, Jiao H, Feng Z . Whole exome sequencing identifies a novel EMD mutation in a Chinese family with dilated cardiomyopathy. BMC Med Genet. 2014; 15:77. PMC: 4105140. DOI: 10.1186/1471-2350-15-77. View

10.

Okita K, Ichisaka T, Yamanaka S . Generation of germline-competent induced pluripotent stem cells. Nature. 2007; 448(7151):313-7. DOI: 10.1038/nature05934. View

11.

Kim C, Majdi M, Xia P, Wei K, Talantova M, Spiering S . Non-cardiomyocytes influence the electrophysiological maturation of human embryonic stem cell-derived cardiomyocytes during differentiation. Stem Cells Dev. 2009; 19(6):783-95. PMC: 3135229. DOI: 10.1089/scd.2009.0349. View

12.

Pant T, Mishra M, Bai X, Ge Z, Bosnjak Z, Dhanasekaran A . Microarray analysis of long non-coding RNA and mRNA expression profiles in diabetic cardiomyopathy using human induced pluripotent stem cell-derived cardiomyocytes. Diab Vasc Dis Res. 2018; 16(1):57-68. DOI: 10.1177/1479164118813888. View

13.

Li W, Ding S . Small molecules that modulate embryonic stem cell fate and somatic cell reprogramming. Trends Pharmacol Sci. 2009; 31(1):36-45. DOI: 10.1016/j.tips.2009.10.002. View

14.

Bagnall R, Molloy L, Kalman J, Semsarian C . Exome sequencing identifies a mutation in the ACTN2 gene in a family with idiopathic ventricular fibrillation, left ventricular noncompaction, and sudden death. BMC Med Genet. 2014; 15:99. PMC: 4355500. DOI: 10.1186/s12881-014-0099-0. View

15.

Almomani R, Verhagen J, Herkert J, Brosens E, Spaendonck-Zwarts K, Asimaki A . Biallelic Truncating Mutations in ALPK3 Cause Severe Pediatric Cardiomyopathy. J Am Coll Cardiol. 2016; 67(5):515-25. DOI: 10.1016/j.jacc.2015.10.093. View

16.

Fassone E, Taanman J, Hargreaves I, Sebire N, Cleary M, Burch M . Mutations in the mitochondrial complex I assembly factor NDUFAF1 cause fatal infantile hypertrophic cardiomyopathy. J Med Genet. 2011; 48(10):691-7. DOI: 10.1136/jmedgenet-2011-100340. View

17.

Holmes D . Stem cell scientists share 2012 Nobel Prize for medicine. Lancet. 2012; 380(9850):1295. DOI: 10.1016/s0140-6736(12)61743-7. View

18.

Janin A, Bessiere F, Chauveau S, Chevalier P, Millat G . First identification of homozygous truncating CSRP3 variants in two unrelated cases with hypertrophic cardiomyopathy. Gene. 2018; 676:110-116. DOI: 10.1016/j.gene.2018.07.036. View

19.

Gherghiceanu M, Barad L, Novak A, Reiter I, Itskovitz-Eldor J, Binah O . Cardiomyocytes derived from human embryonic and induced pluripotent stem cells: comparative ultrastructure. J Cell Mol Med. 2011; 15(11):2539-51. PMC: 3822963. DOI: 10.1111/j.1582-4934.2011.01417.x. View

20.

Fatkin D, MacRae C, Sasaki T, WOLFF M, Porcu M, Frenneaux M . Missense mutations in the rod domain of the lamin A/C gene as causes of dilated cardiomyopathy and conduction-system disease. N Engl J Med. 1999; 341(23):1715-24. DOI: 10.1056/NEJM199912023412302. View