Activation of Mitochondria in Mesenchymal Stem Cells by Mitochondrial Delivery of Coenzyme Q₁₀

抄録

The efficacy of mesenchymal stem cell (MSC) transplantation has been reported for various diseases. We previously developed a drug delivery system targeting mitochondria (MITO-Porter) by using a microfluidic device to encapsulate Coenzyme Q₁₀ (CoQ₁₀) on a large scale. The current study aimed to confirm if treatment with CoQ₁₀ encapsulated by MITO-Porter enhanced mitochondrial functions in MSCs, with the potential to improve MSC transplantation therapy. We used highly purified human bone marrow-derived MSCs, described as rapidly expanding clones (RECs), and attempted to control and increase the amount of CoQ₁₀ encapsulated in the MITO-Porter using microfluidic device system. We treated these RECs with CoQ₁₀ encapsulated MITO-Porter, and evaluated its cellular uptake, co-localization with mitochondria, changes in mitochondrial respiratory capacity, and cellular toxicity. There was no significant change in mitochondrial respiratory capacity following treatment with the previous CoQ₁₀ encapsulated MITO-Porter; however, mitochondrial respiratory capacity in RECs was significantly increased by treatment with CoQ₁₀-rich MITO-Porter. Utilization of a microfluidic device enabled the amount of CoQ₁₀ encapsulated in MITO-Porter to be controlled, and treatment with CoQ₁₀-rich MITO-Porter successfully activated mitochondrial functions in MSCs. The MITO-Porter system thus provides a promising tool to improve MSC cell transplantation therapy.