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Updated: Apr 25, 2026
Modeling Mitochondrial Disease Using Brain Organoids: A Focus on Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like Episodes
Published on: October 10, 2025
iPSC generation from PBMCs of a MELAS patient for mitochondrial dysfunction studies
Gautam Sharma1, Abhay Srivastava1, Cheryl Rockman-Greenberg2
1Institute of Cardiovascular Sciences, St. Boniface Hospital Albrechtsen Research Centre, Regenerative Medicine Program, Department of Physiology and Pathophysiology, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Canada.
Abstract:
Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like episodes (MELAS) is a multisystemic mitochondrial disorder primarily caused by a heteroplasmic point mutation at mitochondrial DNA (mtDNA) position 3243 (m.3243A > G) in the MT-TL1 gene, which encodes mitochondrial tRNA^Leu(UUR). In this study, we report the successful reprogramming of peripheral blood mononuclear cells (PBMCs) from a male patient diagnosed with MELAS into induced pluripotent stem cells (iPSCs). This patient-specific iPSC platform enables investigation into the relationship between heteroplasmy levels and disease manifestation and provides a valuable tool for screening potential therapeutic strategies aimed at mitigating mitochondrial dysfunction in MELAS.
Insights
Researchers successfully reprogrammed patient cells into induced pluripotent stem cells (iPSCs) for studying Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like episodes (MELAS). This creates a platform for understanding disease mechanisms and testing therapies.
Area of Science:
- Biomedical Research
- Genetics
- Cell Biology
Background:
- Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like episodes (MELAS) is a severe multisystemic disorder.
- It is primarily caused by the m.3243A>G mutation in the MT-TL1 gene, affecting mitochondrial tRNA^Leu(UUR).
- Understanding the link between heteroplasmy levels and disease severity is crucial.
Purpose of the Study:
- To generate patient-specific induced pluripotent stem cells (iPSCs) from a MELAS patient.
- To establish a cellular model for investigating MELAS pathogenesis.
- To create a platform for screening potential therapeutic interventions.
Main Methods:
- Reprogramming of peripheral blood mononuclear cells (PBMCs) from a MELAS patient.
- Generation of induced pluripotent stem cells (iPSCs).
- Characterization of patient-derived iPSCs.
Main Results:
- Successful reprogramming of PBMCs into iPSCs from a MELAS patient.
- Establishment of a patient-specific iPSC line.
- The iPSC platform allows for heteroplasmy level analysis.
Conclusions:
- Patient-derived iPSCs provide a valuable model for MELAS research.
- This platform facilitates the study of genotype-phenotype correlations in MELAS.
- It offers a novel avenue for therapeutic strategy screening for mitochondrial dysfunction.
