Stem cells and mitochondria //
Mitochondria are cellular powerplants that produce energy in the form of ATP for the cells needs. In addition to the energy production, mitochondria serve fundamental roles in cellular signaling, generating and regulating reactive oxygen species (ROS), buffering cytosolic calcium levels and regulating apoptosis. Mitochondria are dynamic organelles that undergo active fission and fusion and both mitochondrial mass and activity are regulated constantly.
Mitochondria possess multiple copies of their own DNA and are under dual genetic control by nuclear genome and their own genome.
Mitochondria play a role in several human disorders, and since both nuclear and mitochondrial DNA encode mitochondrial proteins, mutations in both genomes can lead to mitochondrial disorders. The manifestations of these diseases vary from infantile multisystem disorders to adult-onset myopathies and neurodegeneration, and indeed, mitochondrial disease can occur in any organ-system, with any age of onset. The most commonly affected tissues are those that need most energy, namely the brain and the heart.
Cells contain hundreds of mitochondria, each of which contains hundreds of copies of mtDNA. When a mutation occurs in mtDNA, it creates a mixed population of normal and mutant mtDNA, a state called heteroplasmy, which is typical for pathogenic mtDNA mutations. A threshold for an mtDNA mutation, meaning the amount of mutant mtDNA needed to manifest as respiratory chain deficiency and disease, can vary between tissues and individuals.
The pathological mechanisms underlying mitochondrial disease mechanisms are largely unknown. This is mainly due to the lack of proper experimental model systems. Introduction of exogenous DNA to mitochondria has been unsuccessful, preventing generation of animal models. Better experimental models are needed for mtDNA disorders, because of the common occurrence of mtDNA mutations, their highly tissue-specific phenotypes and unknown disease mechanisms.
Stem cell derived models
Induced pluripotent stem (iPS) cells are somatic cells that have been reprogrammed back to a pluripotent stem cell stage. Similarly to embryonic stem cells, they can differentiate to any cell type found in the adult body. Since they can be derived from patients, they have opened up new ways to use patient cells in research. Using this technology it is possible to study disease mechanisms in living patient neurons or cardiac cells, or any other cell type that would otherwise not be available for research purposes.
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