Reviving mitochondria to restore the mind: stem cell-based bioenergetic rescue in Parkinson’s disease

Parkinson's disease is a neurodegenerative disorder of aging with dopaminergic neuronal degeneration in the substantia nigra leading to motor dysfunction. Mitochondrial dysfunction is central to its pathophysiology, leading to oxidative stress, derangement of energy metabolism, and induction of neuronal apoptosis. Current therapeutic interventions are symptomatic but fail to stop disease progression. Stem cell-based regenerative strategies have been recognized as potential disease-modifying treatments. Mitochondria-augmented stem cell therapy offers a new mechanism for the correction of cellular bioenergetic deficits. Through genetic manipulations or preconditioning protocols, mesenchymal stem cells and induced pluripotent stem cells are engineered to enhance mitochondrial function and transfer. The engineered cells enable delivery of functional mitochondria into damaged neurons through tunneling nanotubes or extracellular vesicles, promoting ATP production, inhibiting reactive oxygen species, and restoring mitophagy. Preclinical models have demonstrated improved neuronal survival and motor function, and novel technologies like CRISPR gene editing and 3D bioprinting offer improved translational relevance.