講演情報
[I-AEPCYIA-3]Enhancing Mesenchymal Stem Cells with a Mitochondria-Targeted Drug Delivery System for Cardiac Disease Treatment
○Yuji Maruo1, Masahiro Shiraishi2, Mitsue Hibino3, Daisuke Sasaki2, Jiro Abe2, Atsuhito Takeda2, Yuma Yamada4 (1.Department of Pediatrics, Graduate School of Medicine, Hokkaido University, Sapporo, Japan, 2.Faculty of Pharmaceutical Science, Hokkaido University, Japan, 3.Faculty of Pharmaceutical Science, Hokkaido University ; Japan Science and Technology Agency (JST) Fusion Oriented Research for Disruptive Science and Technology (FOREST) Program)
キーワード：
Mesenchymal stem cell、Coenzyme Q10、Drug delivery system
INTRODUCTION:We successfully developed mitochondria-activated cardiac-derived cells (MITO cells) by introducing mitochondrial functional molecules, such as resveratrol and coenzyme Q10 (CoQ10), into cardiac-derived cell mitochondria using the MITO-Porter system, a mitochondria-targeted drug delivery system. Previous studies demonstrated that transplantation of MITO cell in doxorubicin-induced cardiomyopathy model mice and myocardial ischemia-reperfusion injury model mice and rats exhibited superior preventive and therapeutic effects compared to conventional cell transplantation therapy. However, for clinical applications, it is necessary to identify transplantable stem cells that can be mass-produced and offer greater versatility. To address this issue, we focused on mesenchymal stem cells (MSCs), which are progressing toward clinical use. The efficacy of MSC transplantation therapy has been reported in various diseases, including cardiac conditions. The objective of this study was to validate whether treatment with CoQ10 encapsulated within the MITO-Porter system enhances mitochondrial functions in MSCs, thereby improving the potential efficacy of MSC transplantation therapy.
METHODS:In this study, we used highly purified human bone marrow-derived mesenchymal stem cells, referred to as rapidly expanding clones (RECs). We treated RECs with CoQ10 encapsulated within the MITO-Porter system, and their cellular uptake was evaluated by flow cytometry. We assessed intracellular localization using confocal laser scanning microscopy, while changes in mitochondrial respiratory capacity were evaluated using an extracellular flux analyzer.
RESULTS:Flow cytometry revealed that cellular uptake of CoQ10 encapsulated within the MITO-Porter was significantly increased compared to the non-treatment group. Confocal laser scanning microscopy demonstrated co-localization of fluorescent signals, with yellow signals indicating overlap between mitochondria labeled with a red fluorophore and the MITO-Porter labeled with a green fluorophore. Treatment with CoQ10 encapsulated within the MITO-Porter significantly enhanced mitochondrial respiratory capacity as measured by the extracellular flux analyzer.
CONCLUSIONS:Treatment with CoQ10 encapsulated within the MITO-Porter system effectively enhanced the mitochondrial respiratory capacity in MSCs. The MITO-Porter system represents a promising approach to improve MSC transplantation therapy. Future studies will focus on evaluating the therapeutic efficacy of mitochondria-activated MSCs in cardiac diseases models through in vivo experiments.
METHODS:In this study, we used highly purified human bone marrow-derived mesenchymal stem cells, referred to as rapidly expanding clones (RECs). We treated RECs with CoQ10 encapsulated within the MITO-Porter system, and their cellular uptake was evaluated by flow cytometry. We assessed intracellular localization using confocal laser scanning microscopy, while changes in mitochondrial respiratory capacity were evaluated using an extracellular flux analyzer.
RESULTS:Flow cytometry revealed that cellular uptake of CoQ10 encapsulated within the MITO-Porter was significantly increased compared to the non-treatment group. Confocal laser scanning microscopy demonstrated co-localization of fluorescent signals, with yellow signals indicating overlap between mitochondria labeled with a red fluorophore and the MITO-Porter labeled with a green fluorophore. Treatment with CoQ10 encapsulated within the MITO-Porter significantly enhanced mitochondrial respiratory capacity as measured by the extracellular flux analyzer.
CONCLUSIONS:Treatment with CoQ10 encapsulated within the MITO-Porter system effectively enhanced the mitochondrial respiratory capacity in MSCs. The MITO-Porter system represents a promising approach to improve MSC transplantation therapy. Future studies will focus on evaluating the therapeutic efficacy of mitochondria-activated MSCs in cardiac diseases models through in vivo experiments.