Mitochondria and mtDNA
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. Mitochondrial function also regulates cellular fate choices and is especially important in stem cells regulating quiescence, activation, self-renewal and differentiation of the stem cell pools.
Mitochondria possess multiple copies of their own DNA and are under dual genetic control by nuclear genome and their own genome. We are interested in the maintenance of the mtDNA and the importance of mtDNA integrity in regulating aging and self-renewal of stem cell pools.
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.
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. Stem cell-derived technology allows optimal usage of patient material and generation of in vitro models of those cell types that are relevant for the disease phenotype.
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.
We are developing novel stem cell based model systems, including a human cell-based model for the blood-brain barrier where stem cell-derived cells are combined with microfluidic devices and novel biomaterials.