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Assessment of temporal functional changes and miRNA profiling of human iPSC-derived cardiomyocytes
Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have been developed for cardiac cell transplantation studies more than a decade ago. In order to establish the hiPSC-CM-based platform as an autologous source for cardiac repair and drug toxicity, it is vital to understand the fu...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6742647/ https://www.ncbi.nlm.nih.gov/pubmed/31515494 http://dx.doi.org/10.1038/s41598-019-49653-5 |
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author | Kumar, Naresh Dougherty, Julie A. Manring, Heather R. Elmadbouh, Ibrahim Mergaye, Muhamad Czirok, Andras Greta Isai, Dona Belevych, Andriy E. Yu, Lianbo Janssen, Paul M. L. Fadda, Paolo Gyorke, Sandor Ackermann, Maegen A. Angelos, Mark G. Khan, Mahmood |
author_facet | Kumar, Naresh Dougherty, Julie A. Manring, Heather R. Elmadbouh, Ibrahim Mergaye, Muhamad Czirok, Andras Greta Isai, Dona Belevych, Andriy E. Yu, Lianbo Janssen, Paul M. L. Fadda, Paolo Gyorke, Sandor Ackermann, Maegen A. Angelos, Mark G. Khan, Mahmood |
author_sort | Kumar, Naresh |
collection | PubMed |
description | Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have been developed for cardiac cell transplantation studies more than a decade ago. In order to establish the hiPSC-CM-based platform as an autologous source for cardiac repair and drug toxicity, it is vital to understand the functionality of cardiomyocytes. Therefore, the goal of this study was to assess functional physiology, ultrastructural morphology, gene expression, and microRNA (miRNA) profiling at Wk-1, Wk-2 & Wk-4 in hiPSC-CMs in vitro. Functional assessment of hiPSC-CMs was determined by multielectrode array (MEA), Ca(2+) cycling and particle image velocimetry (PIV). Results demonstrated that Wk-4 cardiomyocytes showed enhanced synchronization and maturation as compared to Wk-1 & Wk-2. Furthermore, ultrastructural morphology of Wk-4 cardiomyocytes closely mimicked the non-failing (NF) adult human heart. Additionally, modulation of cardiac genes, cell cycle genes, and pluripotency markers were analyzed by real-time PCR and compared with NF human heart. Increasing expression of fatty acid oxidation enzymes at Wk-4 supported the switching to lipid metabolism. Differential regulation of 12 miRNAs was observed in Wk-1 vs Wk-4 cardiomyocytes. Overall, this study demonstrated that Wk-4 hiPSC-CMs showed improved functional, metabolic and ultrastructural maturation, which could play a crucial role in optimizing timing for cell transplantation studies and drug screening. |
format | Online Article Text |
id | pubmed-6742647 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-67426472019-09-26 Assessment of temporal functional changes and miRNA profiling of human iPSC-derived cardiomyocytes Kumar, Naresh Dougherty, Julie A. Manring, Heather R. Elmadbouh, Ibrahim Mergaye, Muhamad Czirok, Andras Greta Isai, Dona Belevych, Andriy E. Yu, Lianbo Janssen, Paul M. L. Fadda, Paolo Gyorke, Sandor Ackermann, Maegen A. Angelos, Mark G. Khan, Mahmood Sci Rep Article Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have been developed for cardiac cell transplantation studies more than a decade ago. In order to establish the hiPSC-CM-based platform as an autologous source for cardiac repair and drug toxicity, it is vital to understand the functionality of cardiomyocytes. Therefore, the goal of this study was to assess functional physiology, ultrastructural morphology, gene expression, and microRNA (miRNA) profiling at Wk-1, Wk-2 & Wk-4 in hiPSC-CMs in vitro. Functional assessment of hiPSC-CMs was determined by multielectrode array (MEA), Ca(2+) cycling and particle image velocimetry (PIV). Results demonstrated that Wk-4 cardiomyocytes showed enhanced synchronization and maturation as compared to Wk-1 & Wk-2. Furthermore, ultrastructural morphology of Wk-4 cardiomyocytes closely mimicked the non-failing (NF) adult human heart. Additionally, modulation of cardiac genes, cell cycle genes, and pluripotency markers were analyzed by real-time PCR and compared with NF human heart. Increasing expression of fatty acid oxidation enzymes at Wk-4 supported the switching to lipid metabolism. Differential regulation of 12 miRNAs was observed in Wk-1 vs Wk-4 cardiomyocytes. Overall, this study demonstrated that Wk-4 hiPSC-CMs showed improved functional, metabolic and ultrastructural maturation, which could play a crucial role in optimizing timing for cell transplantation studies and drug screening. Nature Publishing Group UK 2019-09-12 /pmc/articles/PMC6742647/ /pubmed/31515494 http://dx.doi.org/10.1038/s41598-019-49653-5 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Kumar, Naresh Dougherty, Julie A. Manring, Heather R. Elmadbouh, Ibrahim Mergaye, Muhamad Czirok, Andras Greta Isai, Dona Belevych, Andriy E. Yu, Lianbo Janssen, Paul M. L. Fadda, Paolo Gyorke, Sandor Ackermann, Maegen A. Angelos, Mark G. Khan, Mahmood Assessment of temporal functional changes and miRNA profiling of human iPSC-derived cardiomyocytes |
title | Assessment of temporal functional changes and miRNA profiling of human iPSC-derived cardiomyocytes |
title_full | Assessment of temporal functional changes and miRNA profiling of human iPSC-derived cardiomyocytes |
title_fullStr | Assessment of temporal functional changes and miRNA profiling of human iPSC-derived cardiomyocytes |
title_full_unstemmed | Assessment of temporal functional changes and miRNA profiling of human iPSC-derived cardiomyocytes |
title_short | Assessment of temporal functional changes and miRNA profiling of human iPSC-derived cardiomyocytes |
title_sort | assessment of temporal functional changes and mirna profiling of human ipsc-derived cardiomyocytes |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6742647/ https://www.ncbi.nlm.nih.gov/pubmed/31515494 http://dx.doi.org/10.1038/s41598-019-49653-5 |
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