Mesenchymal stem cell (MSC)
transplantation offers significant potential for the treatment of
diabetes mellitus (DM) and its complications. However, hyperglycemic conditions can induce senescence and dysfunction in both transplanted and resident MSCs, thereby limiting their therapeutic potential.
Mitochondrial dysfunction and oxidative stress are key contributors to this process in MSCs exposed to
hyperglycemia. As such, strategies aimed at mitigating
mitochondrial dysfunction could enhance the therapeutic efficacy of MSC
transplantation in DM. In this review, we provide an updated overview of how
mitochondrial dysfunction mediates MSC senescence. We present experimental evidence for the molecular mechanisms behind high
glucose-induced
mitochondrial dysfunction in MSCs, which include impairment of mitochondrial biogenesis, mitochondrial
calcium regulation, the mitochondrial
antioxidant system, mitochondrial fusion-fission dynamics, mitophagy, and intercellular mitochondrial transfer. Furthermore, we propose potential pharmacological candidates that could improve the efficacy of MSC
transplantation by enhancing mitochondrial function in patients with DM and related complications.