Mitochondrial Transplantation Suppressed Muscle Inflammation and Improved the Mitochondrial Dysfunction in C Protein-induced Myositis Model

Jeong Yeon Kim¹, Seon Uk Kim ², Ji soo Park ¹, Ji Hye Lee ³, Jae Hwan Shin ⁴, Do Wan Hwang ⁵, Yun Sang Lee ⁴, Jin Chul Paeng ⁴, Yong Soo Choi ⁶, Jung Wook hwang ⁷, Kyuboem Han ⁸, Chun Hyung Kim ⁸, Mi Jin Kim ⁸, Yeong-Wook Song ⁹ and Eun Young Lee ¹⁰, ¹Division of Rheumatology, Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea., Seoul, Republic of Korea, ²Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, and College of Medicine, Seoul National University, Seoul, Republic of Korea, ³Division of Rheumatology, Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea., Seoul, Republic of Korea, ⁴Department of Nuclear Medicine, Seoul National University Hospital, Seoul, Republic of Korea, ⁵Department of Nuclear Medicine, Seoul National University Hospital, Seoul, Korea., Seoul, Republic of Korea, ⁶Department of Biotechnology, CHA University, Seongnam, Korea, Seongnam, Republic of Korea, ⁷Department of Biotechnology, CHA University, Seongnam, Korea., Seongnam, Republic of Korea, ⁸PAEAN Biotechnology Inc., Daejeon, Korea, Daejeon, Republic of Korea, ⁹Seoul National University Hospital, Seoul, Republic of Korea, ¹⁰Division of Rheumatology, Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea, Seoul, Republic of Korea

Meeting: 2019 ACR/ARP Annual Meeting

Keywords: [18F]FDG PET, C protein-induced myositis, MRI and Mitochondrial transplantation, polymyositis, skeletal muscle inflammation

Session Information

Date: Sunday, November 10, 2019

Title: T Cell Biology & Targets in Autoimmune & Inflammatory Disease Poster

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.

Disclosure: J. Kim, None; S. Kim, None; J. Park, None; J. Lee, None; J. Shin, None; D. Hwang, None; Y. Lee, None; J. Paeng, None; Y. Choi, None; J. hwang, None; K. Han, None; C. Kim, None; M. Kim, None; Y. Song, Astellas Pharma, Inc., 9; E. Lee, None.

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 .

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