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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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Autores principales: Bekhite, Mohamed M., Schulze, P. Christian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8699880/
https://www.ncbi.nlm.nih.gov/pubmed/34943991
http://dx.doi.org/10.3390/cells10123483
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author Bekhite, Mohamed M.
Schulze, P. Christian
author_facet Bekhite, Mohamed M.
Schulze, P. Christian
author_sort Bekhite, Mohamed M.
collection PubMed
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 pubmed-86998802021-12-24 Human Induced Pluripotent Stem Cell as a Disease Modeling and Drug Development Platform—A Cardiac Perspective Bekhite, Mohamed M. Schulze, P. Christian Cells Review 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. MDPI 2021-12-09 /pmc/articles/PMC8699880/ /pubmed/34943991 http://dx.doi.org/10.3390/cells10123483 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Bekhite, Mohamed M.
Schulze, P. Christian
Human Induced Pluripotent Stem Cell as a Disease Modeling and Drug Development Platform—A Cardiac Perspective
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 Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8699880/
https://www.ncbi.nlm.nih.gov/pubmed/34943991
http://dx.doi.org/10.3390/cells10123483
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