Next Article in Journal
Retinoids as Chemo-Preventive and Molecular-Targeted Anti-Cancer Therapies
Next Article in Special Issue
Mitochondria-Induced Immune Response as a Trigger for Neurodegeneration: A Pathogen from Within
Previous Article in Journal
Ganciclovir and Its Hemocompatible More Lipophilic Derivative Can Enhance the Apoptotic Effects of Methotrexate by Inhibiting Breast Cancer Resistance Protein (BCRP)
Previous Article in Special Issue
Mitochondrial Heteroplasmy Shifting as a Potential Biomarker of Cancer Progression
Review

Modelling Mitochondrial Disease in Human Pluripotent Stem Cells: What Have We Learned?

1
Murdoch Children’s Research Institute, Royal Children’s Hospital, Parkville, VIC 3052, Australia
2
Department of Paediatrics, University of Melbourne, Parkville, VIC 3052, Australia
3
Victorian Clinical Genetics Services, Royal Children’s Hospital, Parkville, VIC 3052, Australia
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editors: María Eugenia Soriano and Carlo Viscomi
Int. J. Mol. Sci. 2021, 22(14), 7730; https://doi.org/10.3390/ijms22147730
Received: 30 June 2021 / Revised: 16 July 2021 / Accepted: 16 July 2021 / Published: 20 July 2021
(This article belongs to the Special Issue Molecular Research on Mitochondrial Dysfunction)
Mitochondrial diseases disrupt cellular energy production and are among the most complex group of inherited genetic disorders. Affecting approximately 1 in 5000 live births, they are both clinically and genetically heterogeneous, and can be highly tissue specific, but most often affect cell types with high energy demands in the brain, heart, and kidneys. There are currently no clinically validated treatment options available, despite several agents showing therapeutic promise. However, modelling these disorders is challenging as many non-human models of mitochondrial disease do not completely recapitulate human phenotypes for known disease genes. Additionally, access to disease-relevant cell or tissue types from patients is often limited. To overcome these difficulties, many groups have turned to human pluripotent stem cells (hPSCs) to model mitochondrial disease for both nuclear-DNA (nDNA) and mitochondrial-DNA (mtDNA) contexts. Leveraging the capacity of hPSCs to differentiate into clinically relevant cell types, these models permit both detailed investigation of cellular pathomechanisms and validation of promising treatment options. Here we catalogue hPSC models of mitochondrial disease that have been generated to date, summarise approaches and key outcomes of phenotypic profiling using these models, and discuss key criteria to guide future investigations using hPSC models of mitochondrial disease. View Full-Text
Keywords: stem cell; hPSC; iPSC; hESC; CRISPR-Cas9; mtDNA; disease modelling; mitochondrial disease stem cell; hPSC; iPSC; hESC; CRISPR-Cas9; mtDNA; disease modelling; mitochondrial disease
Show Figures

Figure 1

MDPI and ACS Style

McKnight, C.L.; Low, Y.C.; Elliott, D.A.; Thorburn, D.R.; Frazier, A.E. Modelling Mitochondrial Disease in Human Pluripotent Stem Cells: What Have We Learned? Int. J. Mol. Sci. 2021, 22, 7730. https://doi.org/10.3390/ijms22147730

AMA Style

McKnight CL, Low YC, Elliott DA, Thorburn DR, Frazier AE. Modelling Mitochondrial Disease in Human Pluripotent Stem Cells: What Have We Learned? International Journal of Molecular Sciences. 2021; 22(14):7730. https://doi.org/10.3390/ijms22147730

Chicago/Turabian Style

McKnight, Cameron L., Yau C. Low, David A. Elliott, David R. Thorburn, and Ann E. Frazier 2021. "Modelling Mitochondrial Disease in Human Pluripotent Stem Cells: What Have We Learned?" International Journal of Molecular Sciences 22, no. 14: 7730. https://doi.org/10.3390/ijms22147730

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop