Melatonin Alleviates Oxidative Stress-Induced Mitochondrial Dysfunction Through Ameliorating NAD+ Homeostasis of hDPSCs for Cell-Based Therapy

Human dental pulp stem cells (hDPSCs) exhibit amazing therapeutic abilities in a variety of diseases due to their remarkable self-renewal capacity and multi-differentiation potential. However, their therapeutic potential could be weakened by various factors such as oxidative stress in cell survival microenvironment In Vivo. Here, we explored the protective effect and mechanism of melatonin (Mel) on hDPSCs transplanted in a type 1 diabetes mellitus (T1DM) rat model. Nicotinamide adenine dinucleotide (NAD⁺) metabolism and mitochondrial function were remarkably impaired in T1DM rats caused by oxidative stress, while the combination of Mel and post-hDPSCs transplantation could rebalance NAD⁺ homeostasis through regulating NAMPT-NAD⁺-SIRT1 axis. Furthermore, Mel significantly reduced intracellular and mitochondrial reactive oxygen species, and alleviated cell senescence and apoptosis of hDPSCs exposed to hydrogen peroxide through ameliorating NAD⁺ depletion and mitochondrial dysfunction. The protective role of Mel could be extremely essential to stem cells in tissue engineering and regenerative medicine.