Session Type: Poster Session (Sunday)
Session Time: 9:00AM-11:00AM
Background/Purpose: Polymyositis is a chronic inflammatory myopathy associated with lymphocyte infiltration, especially CD8 + T cells to the muscle layer. C protein-induced myositis (CIM) is a murine model of polymyositis (PM). Dexamethasone treatment has an anti-inflammatory effect on polymyositis, but did not improve mitochondrial dysfunction in muscle of CIM mice. In the previous report, mitochondrial function is restored in damaged cells after transfer of mitochondria from human umbilical cord-derived mesenchymal stem cells (UC-MSCs). We investigate whether mitochondrial transplantation may attenuate inflammation and improve mitochondrial dysfunction in CIM model.
Methods: To induce CIM, C57BL/6 mice were immunized with human skeletal muscle C protein fragment. Dexamethasone was administered intraperitoneally at a dose of 0.8 mg/kg/day. Mitochondria from human UC-MSCs were transplanted intravenously on day1 or day7. To evaluate muscle inflammation, 18F-FDG PET/MRI evaluation was performed on day 14. Muscle tissues were stained with hematoxylin and eosin (H&E) for histological evaluation. Pro-inflammatory cytokines were measured by ELISA. The expression of subunits of OXPHOS (oxidative phosphorylation) complexes (I -V) was investigated by immunoblot analysis. To quantitative evaluation of mitochondrial transplantation, the expression of MITO-CO1 and COX4 was evaluated by RT-qPCR.
Results: Mean of histologic summation score of muscles was decreased in day 1 group (0.67 ± 0.60, n = 3), day 7 group (0.75 ± 0.61, n = 10) of mitochondrial transplantation and dexamethasone-treated group (0.5 ± 0.63, n = 10) compared with vehicle (1.5 ± 0.32, n = 7). PET/MRI showed 18F-FDG uptake reduction after mitochondrial transplantation and dexamethasone treatment. IL-6 was reduced in the serum of mitochondrial transplantation and dexamethasone-treated group. However, the protein expression of OXPHOS complex Ⅱ was increased in day 7 group of mitochondrial transplantation compared with vehicle or dexamethasone-treated group. As a quantitative evaluation of mitochondrial transplantation, the expression of human mitochondrial encoded gene, MITO-CO1 was increased without altering the expression of COX4, the nuclear-encoded gene in day 7 group of mitochondrial transplantation and these data suggest that isolated mitochondria from human UC-MSC transplanted into CIM mouse muscle.
Conclusion: Mitochondrial transplantation suppressed muscle inflammation and improved the mitochondrial dysfunction through an increase of mitochondrial activity. These findings suggest that mitochondrial transplantation may be used as a new potential therapeutic strategy for inflammatory myopathy.
To cite this abstract in AMA style:Kim J, Kim S, Park J, Lee J, Shin J, Hwang D, Lee Y, Paeng J, Choi Y, hwang J, Han K, Kim C, Kim M, Song Y, Lee E. Mitochondrial Transplantation Suppressed Muscle Inflammation and Improved the Mitochondrial Dysfunction in C Protein-induced Myositis Model [abstract]. Arthritis Rheumatol. 2019; 71 (suppl 10). https://acrabstracts.org/abstract/mitochondrial-transplantation-suppressed-muscle-inflammation-and-improved-the-mitochondrial-dysfunction-in-c-protein-induced-myositis-model/. Accessed January 18, 2020.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/mitochondrial-transplantation-suppressed-muscle-inflammation-and-improved-the-mitochondrial-dysfunction-in-c-protein-induced-myositis-model/