In order to study in detail the cytopathological mechanisms of mitochondrial diseases and to validate promising therapeutic options, Creative Bioarray is working on the development of new mitochondrial disease modeling systems using iPSC technologies. Our professional technologies and flexible solutions help accelerate our clients' research on the mechanisms and therapeutics of mitochondrial genetic diseases.
iPSC for Modeling Mitochondrial Diseases
Mitochondrial DNA (mtDNA) defects are a common reason for genetic diseases that disrupt cellular energy production. These disorders are clinically and genetically heterogeneous and have a great impact on cell types with high energy requirements in the heart, brain, and kidneys. Viable disease models are critical for elucidating genotype/phenotype relationships and improving disease management. However, the specificity of mitochondrial genetics has hindered the development of modeling of these diseases.
Current non-human models cannot fully encapsulate the human phenotype of known disease genes. In addition, access to disease-associated cell or tissue types from patients is often limited. Recent studies have shown that the application of iPSC technology in disease modeling overcomes these difficulties. The use of hPSC to model mitochondrial diseases in the context of nuclear DNA (nDNA) and mitochondrial DNA (mtDNA) provides a promising platform for alternative drug discovery. The ability of hPSCs to differentiate into clinically relevant cell types allows researchers to study cellular pathogenesis in detail and validate promising therapeutic options.
Fig.1 Key steps and analysis necessary to establish new mtDNA model systems using iPSCs. (Prigione, 2015)
Our Solutions
Researchers at Creative Bioarray are committed to building iPSC from patients affected by mtDNA disease to correctly resolve the interaction between the nuclear and mitochondrial genomes in appropriate human target cell types. The solutions we offer our clients include, but are not limited to:
- Disease modeling and selection of controls for comparison.
- Quality control and characterization of iPSC disease models.
- Rescue of the disease phenotype.
Use gene-editing methods such as CRISPR-Cas9 to generate patient-corrected isogenic controls or to reconstruct patient mutations in wild-type genetic backgrounds. We have used this technology to successfully generate multiple hPSC models of mitochondrial disease.
We offer multiple validation steps to ensure the quality of hPSC models for mitochondrial diseases, such as normal cell morphology, mycoplasma, normal karyotype, teratoma, or pluripotency screening by directed differentiation into three germ layers.
We use functional analysis techniques for high-throughput screening to identify or validate candidate treatment options, such as compounds, gene therapies, targeted nanoparticle methods, or CRISPR-cas9 screening to accurately locate the target pathways.
Advantages
- Professional technical support
- Customized and reasonable experimental plan
- Short experiment period and one-stop service
With a specialized technology platform, Creative Bioarray has built multiple mitochondrial disease hPSC models to provide clients with a system to study the pathological mechanisms relevant to disease genes or mutations in tissues associated with clinical phenotypes. Our innovative solutions will accelerate your research. If you need our services, please contact us.
Reference
- Prigione, A. Induced pluripotent stem cells (iPSCs) for modeling mitochondrial DNA disorders. Methods in Molecular Biology. 2015, 1265:349-356.