Generation of Mitochondrial-Activated Amnion-Derived Mesenchymal Stromal Cells via a Mitochondrial Coenzyme Q₁₀ Delivery Strategy

Abstract

Mesenchymal stromal cell transplantation therapy has been widely studied in regenerative medicine for the treatment of various diseases. We previously developed a mitochondria-targeted drug delivery system, termed the MITO-Porter, which enables large-scale production of coenzyme Q₁₀ (CoQ₁₀)-encapsulated carriers. This study aimed to generate mitochondrial-activated amnion-derived mesenchymal stromal cells (AMSCs) by delivering CoQ₁₀ to mitochondria using the MITO-Porter system, with the potential to improve AMSC transplantation outcomes. We treated AMSCs with CoQ₁₀-encapsulated MITO-Porter and evaluated cellular uptake, co-localization with mitochondria, changes in mitochondrial respiratory capacity, and antioxidant capacity. CoQ₁₀-encapsulated MITO-Porter was internalized by AMSCs and co-localized with mitochondria. Treatment of AMSCs with CoQ₁₀-encapsulated MITO-Porter significantly increased the mitochondrial oxygen consumption rate and decreased superoxide levels. Mitochondrial delivery of CoQ₁₀ successfully enhanced the mitochondrial respiratory capacity and antioxidant ability of AMSCs. These mitochondrial-activated AMSCs, newly generated using the MITO-Porter system, represent a promising cell source for improving MSC-based transplantation therapy.