Oxidative stress resistant cells for transplantation
October 2016
Mayo Clinic, Jacksonville, USA
Parkinson's disease is a devastating neurodegenerative disorder that results in a massive dopaminergic neuronal loss that leads to motor dysfunction, cognitive decline and, ultimately, death. Many factors have been described as a potential cause leading to the death of neurons, such as oxidative stress. The overproduction of reactive oxygen species can lead to DNA damage, and this has been proposed to be a major cause of dopaminergic neuronal death in Parkinson's patients. In recent years, cell replacement therapy has arisen as a potential therapeutic solution. However, cell survival is limited due to the neurotoxic environment present in the areas of transplantation. Here, a new approach is developed to increase cell survival upon transplantation by introducing a mutated H2AX gene to induce DNA repair and avoid apoptosis. The results show that dopaminergic neuron-like cells obtained from bone marrow-derived mesenchymal stromal cells with expression of the mutated H2AX have higher resistance to DNA damage and decreased levels of apoptosis after exposure to ultraviolet radiation or MPP+ treatment. In this study, the researchers develop a new strategy to obtain neuron-like cells that are more resistant to neurotoxic environments, which has great potential in developing cell replacement applications in neurodegenerative diseases.
Genetic modification of H2AX renders mesenchymal stromal cell–derived dopamine neurons more resistant to DNA damage and subsequent apoptosis
Dennis W Dickson, Peizhou Jiang
Added on: 09-01-2021
[1] https://www.isct-cytotherapy.org/article/S1465-3249(16)30497-2/fulltext[2] https://data.jrc.ec.europa.eu/dataset/a8fd26ef-b113-47ab-92ba-fd2be449c7eb
