(Multipotent mesenchymal stromal cells MSCs) (AAV) MSCs. DMD IL-10 -/- mdx. in vivo. mdx. IL-10 -/- mdx mdx M1 IL-6 DMD. mdx.

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2 (Multipotent mesenchymal stromal cellsmscs) (Duchenne) (DMD) 1) DMD mdx / utro -/- /mdx 2) MSCs MSCs DMD (Kasahara et al., 2012) IL-10 Th2 CD4 + T IL-6 IL-10 IL-10 DMD (IL-10 -/- /mdx) MSCs DMD MSCs IL-10 MSCs IL-10 DMD IL-10 -/- mdx (AAV) IL-10 MSCs in vivo DMD IL-10 -/- mdx mdx M1 IL-6 mdx IL-10 -/- mdx (%FS) IL-10 mdx DMD IL-10 IL-10 (AAV) MSCs MSCs IL-10 MSCs AAV IL-10 MSCs 70 MSCs IL-10 8~12 MSCs MSCs IL-10 mdx DMD IL-10 MSCs MSCs IL-10 MSCs MSCs

3 1. Yuko Nitahara-Kasahara, Hiromi Hayashita-Kinoh, Tomoko Chiyo, Akiyo Nishiyama, Hironori Okada, Shin ichi Takeda and Takashi Okada. Dystrophic mdx mice develop severe cardiac and respiratory dysfunction following genetic ablation of the anti-inflammatory cytokine IL-10. Hum. Mol. Gen. 23(15): , Yuko Nitahara-Kasahara, Shin ichi Takeda and Takashi Okada. : Cell therapeutic approaches using multipotent mesencymal stromal cells for muscular dystrophy. Inflammation and Regeneration. Vol. 34, No.4, p Yuko Nitahara-Kasahara. Shin ichi Takeda and Takashi Okada. Inflammatory predisposition predicts disease phenotypes in muscular dystrophy. Inflammation and Regeneration. Inflammation and Regeneration. Vol. 36, No.14, Janek Hyzewicz, Jun Tanihata, Mutsuki Kuraoka, Yuko Nitahara-Kasahara, Teiva Beylier, Urs T Ruegg, Axel Vater, Shin ichi Takeda. Low intensity training and the C5a complement antagonist NOX-D21 rescue the mdx phenotype through modulation of inflammation. American Journal of Pathology, In printing, Yuko Nitahara-Kasahara, Hiromi Hayashita-Kinoh, Nana Tsumita, Hironori Okada, Shin'ichi Takeda and Takashi Okada. Exacerbation in the IL-10 deficient dystrophic mice and an anti-inflammatory strategy with mesenchymal stromal cells. The 13 th International Congress of Human Genetics (Poster presentation), Kyoto, April 6, 2016 (April 3-7). Hiromi Hayashita-Kinoh, Yuko Nitahara-Kasahara, Hironori Okada, Kiwamu Imagawa, Katsuhiko Tachibana, Shin'ichi Takeda,MD,PhD2 and Takashi Okada.Improved transduction of canine X-linked muscular dystrophy with raav9-microdystrophin by MSCs pretreatment. The 13 th International Congress of Human Genetics (Poster presentation), Kyoto, April 6, Hiromi Hayashita-Kinoh, Hironori Okada, Yuko Nitahara-Kasahara, Tomoko Chiyo, Kiwamu Imagawa, Katsuhiko Tachibana, Shin ichi Takeda, Takashi Okada. Improved transduction of canine X-linked muscular dystrophy with raav9-microdystrophin by introducing immune tolerance. 19 th Annual Meeting of American Society of Gene & Cell Therapy (Poster presentation), Washington DC, May 4-7, Hironori Okada, Hidetoshi Ishibashi, Chiaki Masuda, Hiromi Hayashita-Kinoh, Tomoko Chiyo, Yuko Nitahara-Kasahara, Yoko Endo-Takahashi, Koichi Kato, Yoichi Negishi, Shin ichi Takeda, Takashi Okada, Transient Ultrasound-Mediated Microbubble-Assisted Modulation of Blood-Brain Interface in Adult Common Marmoset to Improve raav-mediated Brain Transduction. 19th Annual Meeting of American Society of Gene & Cell Therapy (Poster presentation), Washington DC, May 4-7, Yuko Nitahara-Kasahara, Mutsuki Kuraoka, Hiromi Hayashita Kinoh, Aki Takahashi, Chiaki Masuda, Kiwamu Imagawa, Katsuhiko Tachibana, Shin'ichi Takeda and Takashi Okada. Cell therapeutic approach using dental pulp stromal cells for Duchenne muscular dystrophy. 22 nd Annual Meeting of Japan Society of Gene & Cell Therapy (Oral presentation), Tokyo, July 28, 2016 (July 28-30). Hiromi Hayashita Kinoh, Yuko Nitahara-Kasahara, Mutsuki Kuraoka, Hironori Okada, Chiaki Masuda, Kiwamu Imagawa, Katsuhiko Tachibana, Shin'ichi Takeda and Takashi Okada. Systemic administration of raav9-microdystrophin with MSCs pre-treatment improves transgene expression and expression and phenotype in CXMDJ. 22 nd Annual Therapy (Oral presentation), Tokyo, July 28, Ryo Ikeue, Aki Takahashi, Takashi Muramatsu, Yuko Kasahara, Atsushi Watanabe, Takashi Shimada, Takashi Okada, Toru Sato. Assessment of the alveolar bone and tooth in lethal hypophosphatasia mice treated by raav8-tnalp-d nd Annual Meeting of Japan Society of Gene & Cell Therapy (Oral presentation), Tokyo, July 29, Aki Nakamura-Takahashi, Ryo

4 Ikeue, Yuko Nitahara-Kasahara, Atsushi Watanabe, Yukihiko Hirai, Masataka Kasahara, Takashi Okada. Therapeutic effects of scaav8-mediated high dose expression of bone targeted alkaline phosphatase on the lethal hypophosphatasia mice. 22 nd Annual Therapy (Oral presentation), Tokyo, July 29, Chikako Nito, Kota Sowa, Masataka Nakajima, Masayuki Ueda, Yasuhiro Nishiyama, Satoshi Suda, Aki Nakamura, Kiwamu Imagawa, Katsuhiko Tachibana, Yuko Kasahara, Takashi Okada, Kazumi Kimura. Intravenous administration of dental pulp stem cells in a rat stroke model. 22 nd Annual Meeting of Japan Society of Gene & Cell Therapy (Poster presentation), Tokyo, July 29, ,,,,, 4,, DMD AAV DMD ,,,,,,,,,,,, HGF ,,,,,,,,, HGF Nitahara-Kasahara Y, Hayashita-Kinoh H, Kuraoka M, Chiyo T, Okada H, Tsumita N, Imagawa K, Tachibana K, Takeda S, Okada T. Mesenchymal Stromal Cells Can Ameliorate the Progressive Phenotype of Dog With Duchenne Muscular Dystrophy. 18th Annual Meeting of American Society of Gene & Cell Therapy, New Orleans, Louisiana, May 14,2015. Kasahara Y, Kinoh H, Kuraoka M, Chiyo T, Okada H, Tsumita N, Imagawa K, Tachibana K, Takeda S, Okada T.Mesenchymal stromal cells ameliorate progressive phenotype of Duchenne muscular dystrophy in dog. 22th Annual Therapy,Osaka,July 24, Yuko Nitahara-Kasahara, Hiromi Hayashita-Kinoh, Tomoko Chiyo, Hironori Okada, Takashi Okada, Shin ichi Takeda. Skeletal muscle engraftment of mesenchymal stromal cells is augmented by IL-10. ASGCT 17th Annual Meeting May 21-24, 2014 DC, USA.. Yuko Nitahara-Kasahara, Hiromi Hayashita-Kinoh, Nana Tsumita, Tomoko Chiyo, Hironori Okada, Shin'ichi Takeda and Takashi Okada Engraftment of mesenchymal stromal cells is effectively associated by IL-10 in skeletal muscle. JSGT 20th Annual meeting. Aug 8th, 2014, Tokyo JCR

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