Human Induced Pluripotent Stem Cell as a Disease Modeling and Drug Development Platform—A Cardiac Perspective

A comprehensive understanding of the pathophysiology and cellular responses to drugs in human heart disease is limited by species differences between humans and experimental animals. In addition, isolation of human cardiomyocytes (CMs) is complicated because cells obtained by biopsy do not prolifera...

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Main Authors: Mohamed M. Bekhite, P. Christian Schulze
Format: Article
Language:English
Published: MDPI AG 2021-12-01
Series:Cells
Subjects:
Online Access:https://www.mdpi.com/2073-4409/10/12/3483
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author Mohamed M. Bekhite
P. Christian Schulze
author_facet Mohamed M. Bekhite
P. Christian Schulze
author_sort Mohamed M. Bekhite
collection DOAJ
description A comprehensive understanding of the pathophysiology and cellular responses to drugs in human heart disease is limited by species differences between humans and experimental animals. In addition, isolation of human cardiomyocytes (CMs) is complicated because cells obtained by biopsy do not proliferate to provide sufficient numbers of cells for preclinical studies in vitro. Interestingly, the discovery of human-induced pluripotent stem cell (hiPSC) has opened up the possibility of generating and studying heart disease in a culture dish. The combination of reprogramming and genome editing technologies to generate a broad spectrum of human heart diseases in vitro offers a great opportunity to elucidate gene function and mechanisms. However, to exploit the potential applications of hiPSC-derived-CMs for drug testing and studying adult-onset cardiac disease, a full functional characterization of maturation and metabolic traits is required. In this review, we focus on methods to reprogram somatic cells into hiPSC and the solutions for overcome immaturity of the hiPSC-derived-CMs to mimic the structure and physiological properties of the adult human CMs to accurately model disease and test drug safety. Finally, we discuss how to improve the culture, differentiation, and purification of CMs to obtain sufficient numbers of desired types of hiPSC-derived-CMs for disease modeling and drug development platform.
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spelling doaj.art-6bbc9464d5ff407b9f793df6d0b634872023-11-23T07:38:25ZengMDPI AGCells2073-44092021-12-011012348310.3390/cells10123483Human Induced Pluripotent Stem Cell as a Disease Modeling and Drug Development Platform—A Cardiac PerspectiveMohamed M. Bekhite0P. Christian Schulze1Department of Internal Medicine I, Division of Cardiology, University Hospital Jena, FSU, 07747 Jena, GermanyDepartment of Internal Medicine I, Division of Cardiology, University Hospital Jena, FSU, 07747 Jena, GermanyA comprehensive understanding of the pathophysiology and cellular responses to drugs in human heart disease is limited by species differences between humans and experimental animals. In addition, isolation of human cardiomyocytes (CMs) is complicated because cells obtained by biopsy do not proliferate to provide sufficient numbers of cells for preclinical studies in vitro. Interestingly, the discovery of human-induced pluripotent stem cell (hiPSC) has opened up the possibility of generating and studying heart disease in a culture dish. The combination of reprogramming and genome editing technologies to generate a broad spectrum of human heart diseases in vitro offers a great opportunity to elucidate gene function and mechanisms. However, to exploit the potential applications of hiPSC-derived-CMs for drug testing and studying adult-onset cardiac disease, a full functional characterization of maturation and metabolic traits is required. In this review, we focus on methods to reprogram somatic cells into hiPSC and the solutions for overcome immaturity of the hiPSC-derived-CMs to mimic the structure and physiological properties of the adult human CMs to accurately model disease and test drug safety. Finally, we discuss how to improve the culture, differentiation, and purification of CMs to obtain sufficient numbers of desired types of hiPSC-derived-CMs for disease modeling and drug development platform.https://www.mdpi.com/2073-4409/10/12/3483iPSCcardiomyocytesmetabolic phenotypegenome-editingdisease modelingdrug testing
spellingShingle Mohamed M. Bekhite
P. Christian Schulze
Human Induced Pluripotent Stem Cell as a Disease Modeling and Drug Development Platform—A Cardiac Perspective
Cells
iPSC
cardiomyocytes
metabolic phenotype
genome-editing
disease modeling
drug testing
title Human Induced Pluripotent Stem Cell as a Disease Modeling and Drug Development Platform—A Cardiac Perspective
title_full Human Induced Pluripotent Stem Cell as a Disease Modeling and Drug Development Platform—A Cardiac Perspective
title_fullStr Human Induced Pluripotent Stem Cell as a Disease Modeling and Drug Development Platform—A Cardiac Perspective
title_full_unstemmed Human Induced Pluripotent Stem Cell as a Disease Modeling and Drug Development Platform—A Cardiac Perspective
title_short Human Induced Pluripotent Stem Cell as a Disease Modeling and Drug Development Platform—A Cardiac Perspective
title_sort human induced pluripotent stem cell as a disease modeling and drug development platform a cardiac perspective
topic iPSC
cardiomyocytes
metabolic phenotype
genome-editing
disease modeling
drug testing
url https://www.mdpi.com/2073-4409/10/12/3483
work_keys_str_mv AT mohamedmbekhite humaninducedpluripotentstemcellasadiseasemodelinganddrugdevelopmentplatformacardiacperspective
AT pchristianschulze humaninducedpluripotentstemcellasadiseasemodelinganddrugdevelopmentplatformacardiacperspective