Mitochondrial transfer from bone mesenchymal stem cells protects against tendinopathy both in vitro and in vivo

Abstract

Background Although mesenchymal stem cells (MSCs) have been effective in tendinopathy, the mechanisms by which MSCs promote tendon healing have not been fully elucidated. In this study, we tested the hypothesis that MSCs transfer mitochondria to injured tenocytes in vitro and in vivo to protect against Achilles tendinopathy (AT). Methods Bone marrow MSCs and H2O2-injured tenocytes were co-cultured, and mitochondrial transfer was visualized by MitoTracker dye staining. Mitochondrial function, including mitochondrial membrane potential, oxygen consumption rate, and adenosine triphosphate content, was quantified in sorted tenocytes. Tenocyte proliferation, apoptosis, oxidative stress, and inflammation were analyzed. Furthermore, a collagenase type I-induced rat AT model was used to detect mitochondrial transfer in tissues and evaluate Achilles tendon healing. Results MSCs successfully donated healthy mitochondria to in vitro and in vivo damaged tenocytes. Interestingly, mitochondrial transfer was almost completely blocked by co-treatment with cytochalasin B. Transfer of MSC-derived mitochondria decreased apoptosis, promoted proliferation, and restored mitochondrial function in H2O2-induced tenocytes. A decrease in reactive oxygen species and pro-inflammatory cytokine levels (interleukin-6 and -1β) was observed. In vivo, mitochondrial transfer from MSCs improved the expression of tendon-specific markers (scleraxis, tenascin C, and tenomodulin) and decreased the infiltration of inflammatory cells into the tendon. In addition, the fibers of the tendon tissue were neatly arranged and the structure of the tendon was remodeled. Inhibition of mitochondrial transfer by cytochalasin B abrogated the therapeutic efficacy of MSCs in tenocytes and tendon tissues. Conclusions MSCs rescued distressed tenocytes from apoptosis by transferring mitochondria. This provides evidence that mitochondrial transfer is one mechanism by which MSCs exert their therapeutic effects on damaged tenocytes.

Human Umbilical Cord Mesenchymal Stem Cells promote tendon functional repair in a Collagenase-Induced Tendinopathy Model

“…MMPs play a crucial role in tissue remodeling, and a study on rat exor tendon healing found that MMP-9 is involved in the early stage of collagen I degradation [37]. In our study, protein and transcription levels of matrix metalloproteinase- [35]. We also measured Tenascin C (TNC), a glycoprotein that interacts with collagen bers to maintain ECM mechanical properties [39].…”

Co-culture of STRO1 + human gingival mesenchymal stem cells and human umbilical vein endothelial cells in 3D spheroids: enhanced in vitro osteogenic and angiogenic capacities

“… (v) Mitochondrial Transfer in MSCs: Mitochondrial function is essential in cellular homeostasis and metabolism control. During osteogenic induction, MSCs may engage in intercellular mitochondrial transfer via Gap junction channels (GJCs), cell fusion, EVs, tunneling nanotubes (TNTs), and other mechanisms, consequently promoting osteogenic differentiation and enhancing cell viability in MSCs( Hsu et al, 2016 ; Li et al, 2017 ; Zheng et al, 2020 ; Yan et al, 2021 ; Wei et al, 2023 ). Intriguingly, our results corroborate that introducing HUVECs bolsters cellular ATP activity within GHS and significantly augments osteogenic differentiation.…”