A step forward in disease modelling for mitochondrial diseases

Zambelli, Filippo; Spits, Claudia

doi:10.21037/sci.2017.10.06

Cited by 3 publications

(1 citation statement)

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“…Mitochondrial disease hPSC models provide a system to study disease gene- or mutation-related pathomechanisms in tissues relevant to the clinical phenotype. Ultimately, the long-term goal of these models would be to identify a phenotype in a clinically relevant cell type that could be used to validate efficacy of targeted treatments, or for use in high-throughput treatment trials [ 94 , 95 , 96 ] ( Figure 2 ).…”

Section: Disease Modellingmentioning

confidence: 99%

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

McKnight

Low

Elliott

et al. 2021

IJMS

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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.

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Section: Disease Modellingmentioning

confidence: 99%