徳島大学 / 教育研究者総覧 --- 加納史也

個人のホームページ

https://researchmap.jp/fumiya (researchmap)

専門分野

○	再生医療 (Regenerative Medicine), 神経科学 (Neuroscience), 疼痛制御

研究テーマ

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著書・論文

著書:

1.	加納史也 : デンタルダイヤモンド増刊号臨床現場で役に立つ''痛み''の教科書, 株式会社デンタルダイヤモンド社, 2020年10月. (キーワード) 歯の痛み / 神経障害性疼痛
2.	N Ichimura, N Yamamoto, M Nishikawa, H Sakakura, Fumiya Kano, K Sato, S Yamaguchi and H Hibi : Human papillomavirus related carcinogenesis in oral cancer, 2018.
3.	Kazuto Okabe, Ryuji Kaneko, Kazutada Usami, Takamasa Kawai, Fumiya Kano and Hideharu Hibi : Evaluation of the effect of polaprezinc against oral mucositis associated with concurrent chemoradiotherapy, 2018.
4.	Akihito Yamamoto, Kohki Matsubara, Kiyoshi Sakai, Fumiya Kano and Minoru Ueda : Multifaceted Neuro-Regenerative Activities of Human Dental Pulp Stem Cells for Functional Recovery after Spinal Cord Injury, 2014.
5.	Akihito Yamamoto, Sakai Kiyoshi, Matsubara Kohki, Fumiya Kano and Ueda Minoru : Multifaceted Neuro-Regenerative Activities of Human Dental Pulp Stem Cells for Functional Recovery after Spinal Cord Injury, INTEC, 2014.

学術論文(審査論文):

1.	Linze Xia, Fumiya Kano, Noboru Hashimoto, Yao Liu, Tsendsuren Khurel-Ochir, Naoko Ogasawara, Cheng Ding, Yang Xu, Hideharu Hibi, Tomonori Iwasaki, Eiji Tanaka and Akihito Yamamoto : Conditioned Medium From Stem Cells of Human Exfoliated Deciduous Teeth Alleviates Mouse Osteoarthritis by Inducing sFRP1-Expressing M2 Macrophages., Stem Cells Translational Medicine, Vol.13, No.4, 399-413, 2024. (要約) Intravenous administration of conditioned medium from stem cells of human exfoliated deciduous teeth (SHED-CM) regenerates mechanically injured osteochondral tissues in mouse temporomandibular joint osteoarthritis (TMJOA). However, the underlying therapeutic mechanisms remain unclear. Here, we showed that SHED-CM alleviated injured TMJ by inducing anti-inflammatory M2 macrophages in the synovium. Depletion of M2 by Mannosylated Clodrosome abolished the osteochondral repair activities of SHED-CM. Administration of CM from M2-induced by SHED-CM (M2-CM) effectively ameliorated mouse TMJOA by inhibiting chondrocyte inflammation and matrix degradation while enhancing chondrocyte proliferation and matrix formation. Notably, in vitro, M2-CM directly suppressed the catabolic activities while enhancing the anabolic activities of interleukin-1β-stimulated mouse primary chondrocytes. M2-CM also inhibited receptor activator of nuclear factor NF-κB ligand-induced osteoclastogenesis in RAW264.7 cells. Secretome analysis of M2-CM and M0-CM revealed that 5 proteins related to anti-inflammation and/or osteochondrogenesis were enriched in M2-CM. Of these proteins, the Wnt signal antagonist, secreted frizzled-related protein 1 (sFRP1), was the most abundant and played an essential role in the shift to anabolic chondrocytes, suggesting that M2 ameliorated TMJOA partly through sFRP1. This study suggests that secretome from SHED exerted remarkable osteochondral regeneration activities in TMJOA through the induction of sFRP1-expressing tissue-repair M2 macrophages. (キーワード) Humans / Mice / Animals / Culture Media, Conditioned / Stem Cells / Macrophages / Osteoarthritis / Anti-Inflammatory Agents / Tooth, Deciduous (出版サイトへのリンク) ● Publication site (DOI): 10.1093/stcltm/szae006 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 38366885 ● Summary page in Scopus @ Elsevier: 2-s2.0-85190754023 (DOI: 10.1093/stcltm/szae006, PubMed: 38366885, Elsevier: Scopus)
2.	Linze XIA, Fumiya Kano, Noboru Hashimoto, Cheng DING, Yang XU, Hideharu HIBI, Tomonori Iwasaki, Eiji Tanaka and Akihito Yamamoto : Conditioned Medium from Stem Cells of Human Exfoliated Deciduous Teeth Partially Alters the Expression of Inflammation-associated Molecules of Mouse Condylar Chondrocytes via Secreted Frizzled-related Protein 1, Journal of Oral Health and Biosciences, Vol.35, No.2, 52-60, 2023. (徳島大学機関リポジトリ) ● Metadata: 118150 (出版サイトへのリンク) ● Publication site (DOI): 10.20738/johb.35.2_52 (文献検索サイトへのリンク) ● Search Scopus @ Elsevier (DOI): 10.20738/johb.35.2_52 (徳島大学機関リポジトリ: 118150, DOI: 10.20738/johb.35.2_52)
3.	Fumiya Kano, Noboru Hashimoto, Yao Liu, Linze Xia, Takaaki Nishihara, Wakana Oki, Keita Kawarabayashi, Noriko Mizusawa, Keiko Aota, Takayoshi Sakai, Masayuki Azuma, Hideharu Hibi, Tomonori Iwasaki, Tsutomu Iwamoto, Nobuyasu Horimai and Akihito Yamamoto : Therapeutic benefits of factors derived from stem cells from human exfoliated deciduous teeth for radiation-induced mouse xerostomia, Scientific Reports, Vol.13, No.1, 2706-2719, 2023. (要約) Radiation therapy for head and neck cancers is frequently associated with adverse effects on the surrounding normal tissue. Irreversible damage to radiation-sensitive acinar cells in the salivary gland (SG) causes severe radiation-induced xerostomia (RIX). Currently, there are no effective drugs for treating RIX. We investigated the efficacy of treatment with conditioned medium derived from stem cells from human exfoliated deciduous teeth (SHED-CM) in a mouse RIX model. Intravenous administration of SHED-CM, but not fibroblast-CM (Fibro-CM), prevented radiation-induced cutaneous ulcer formation (p < 0.0001) and maintained SG function (p < 0.0001). SHED-CM treatment enhanced the expression of multiple antioxidant genes in mouse RIX and human acinar cells and strongly suppressed radiation-induced oxidative stress. The therapeutic effects of SHED-CM were abolished by the superoxide dismutase inhibitor diethyldithiocarbamate (p < 0.0001). Notably, quantitative liquid chromatography-tandem mass spectrometry shotgun proteomics of SHED-CM and Fibro-CM identified eight proteins activating the endogenous antioxidant system, which were more abundant in SHED-CM than in Fibro-CM (p < 0.0001). Neutralizing antibodies against those activators reduced antioxidant activity of SHED-CM (anti-PDGF-D; p = 0.0001, anti-HGF; p = 0.003). Our results suggest that SHED-CM may provide substantial therapeutic benefits for RIX primarily through the activation of multiple antioxidant enzyme genes in the target tissue. (キーワード) Mice / Humans / Animals / Antioxidants / Stem Cells / Disease Models, Animal / Xerostomia / Tooth, Deciduous (徳島大学機関リポジトリ) ● Metadata: 118051 (出版サイトへのリンク) ● Publication site (DOI): 10.1038/s41598-023-29176-w (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 36792628 ● Summary page in Scopus @ Elsevier: 2-s2.0-85148115146 (徳島大学機関リポジトリ: 118051, DOI: 10.1038/s41598-023-29176-w, PubMed: 36792628, Elsevier: Scopus)
4.	YAO LIU, Fumiya Kano, Noboru Hashimoto, LINZE XIA, Qiao Zhou, Xingmei Feng, Hideharu Hibi, Aya Miyazaki, Tsutomu Iwamoto, Yoshizo Matsuka, Zhijun Zhang, Eiji Tanaka and Akihito Yamamoto : Conditioned Medium From the Stem Cells of Human Exfoliated Deciduous Teeth Ameliorates Neuropathic Pain in a Partial Sciatic Nerve Ligation Model., Frontiers in Pharmacology, Vol.13, 745020, 2022. (要約) In neuropathic pain (NP), injury or diseases of the somatosensory system often result in highly debilitating chronic pain. Currently, there is no effective drug for the complete and definitive treatment of NP. We investigated the therapeutic potential of conditioned medium (CM) derived from stem cells from human exfoliated deciduous teeth (SHED-CM) against NP using a mouse partial sciatic nerve ligation (PSL) model. Abnormal pain sensation, such as tactile allodynia and hyperalgesia, can be caused by PSL. In the behavioral test, intravenous administration of SHED-CM greatly improved the PSL-induced hypersensitivity. We found that treatment with SHED-CM resulted in the recruitment of M2 macrophages in the injured sciatic nerve and ipsilateral L4/L5 dorsal root ganglion and suppressed microglial activation in the spinal cord. Notably, specific depletion of the anti-inflammatory M2 macrophages by mannosylated-Clodrosome markedly reduced the antinociceptive effect of SHED-CM. Intravenous administration of CM from M2 induced by SHED-CM (M2-CM) ameliorated the PSL-induced hypersensitivity. We found that M2-CM directly suppressed the expression of nociceptive receptors as well as proinflammatory mediators in Schwann cells. Taken together, our data suggest that SHED-CM ameliorates NP through the induction of the analgesic anti-inflammatory M2 macrophages. Thus, SHED-CM may be a novel therapeutic candidate for NP. (徳島大学機関リポジトリ) ● Metadata: 117219 (出版サイトへのリンク) ● Publication site (DOI): 10.3389/fphar.2022.745020 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 35431971 ● Summary page in Scopus @ Elsevier: 2-s2.0-85128452809 (徳島大学機関リポジトリ: 117219, DOI: 10.3389/fphar.2022.745020, PubMed: 35431971, Elsevier: Scopus)
5.	Arief Waskitho, Yumiko Yamamoto, S Raman, Fumiya Kano, Huijiao Yan, R Raju, S Afroz, Tsuyoshi Morita, Daisuke Ikutame, Kazuo Okura, Masamitsu Ohshima, Akihito Yamamoto, Otto Baba and Yoshizo Matsuka : Peripherally Administered Botulinum Toxin Type A Localizes Bilaterally in Trigeminal Ganglia of Animal Model, Toxins, Vol.13, No.10, 704, 2021. (徳島大学機関リポジトリ) ● Metadata: 116383 (出版サイトへのリンク) ● Publication site (DOI): 10.3390/toxins13100704 (文献検索サイトへのリンク) ● Search Scopus @ Elsevier (DOI): 10.3390/toxins13100704 (徳島大学機関リポジトリ: 116383, DOI: 10.3390/toxins13100704)
6.	Hisanori Muto, Takanori Ito, Taku Tanaka, Shinya Yokoyama, Kenta Yamamoto, Norihiro Imai, Yoji Ishizu, Keiko Maeda, Takashi Honda, Tetsuya Ishikawa, Asuka Kato, Taichi Ohshiro, Fumiya Kano, Akihito Yamamoto, Kiyoshi Sakai, Hideharu Hibi, Masatoshi Ishigami and Mitsuhiro Fujishiro : Conditioned medium from stem cells derived from human exfoliated deciduous teeth ameliorates NASH via the GutLiver axis, Scientific Reports, Vol.18778 (2021), No.11, 2021. (要約) Non-alcoholic steatohepatitis (NASH) occurrence has been increasing and is becoming a major cause of liver cirrhosis and liver cancer. However, effective treatments for NASH are still lacking. We examined the benefits of serum-free conditioned medium from stem cells derived from human exfoliated deciduous teeth (SHED-CM) on a murine non-alcoholic steatohepatitis (NASH) model induced by a combination of Western diet (WD) and repeated administration of low doses of carbon tetrachloride intraperitoneally, focusing on the gut-liver axis. We showed that repeated intravenous administration of SHED-CM significantly ameliorated histological liver fibrosis and inflammation in a murine NASH model. SHED-CM inhibited parenchymal cell apoptosis and reduced the activation of inflammatory macrophages. Gene expression of pro-inflammatory and pro-fibrotic mediators (such as Tnf-α, Tgf-β, and Ccl-2) in the liver was reduced in mice treated with SHED-CM. Furthermore, SHED-CM protected intestinal tight junctions and maintained intestinal barrier function, while suppressing gene expression of the receptor for endotoxin, Toll-like receptor 4, in the liver. SHED-CM promoted the recovery of Caco-2 monolayer dysfunction induced by IFN-γ and TNF-α in vitro. Our findings suggest that SHED-CM may inhibit NASH fibrosis via the gut-liver axis, in addition to its protective effect on hepatocytes and the induction of macrophages with unique anti-inflammatory phenotypes. (キーワード) Adult / Animals / Apoptosis / Caco-2 Cells / Culture Media, Conditioned / Gastrointestinal Microbiome / Humans / Intestines / Liver / Macrophage Activation / Mice / Models, Biological / Non-alcoholic Fatty Liver Disease / Stem Cells / Tooth, Deciduous (徳島大学機関リポジトリ) ● Metadata: 117268 (出版サイトへのリンク) ● Publication site (DOI): 10.1038/s41598-021-98254-8 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 34548598 ● Search Scopus @ Elsevier (PMID): 34548598 ● Search Scopus @ Elsevier (DOI): 10.1038/s41598-021-98254-8 (徳島大学機関リポジトリ: 117268, DOI: 10.1038/s41598-021-98254-8, PubMed: 34548598)
7.	Yao Liu, Linze Xia, Fumiya Kano, Noboru Hashimoto, Yoshizo Matsuka, Akihito Yamamoto and Eiji Tanaka : Low-intensity pulsed ultrasound ameliorates neuropathic pain induced by partial sciatic nerve ligation via regulating macrophage polarization, Journal of Oral Health and Biosciences, Vol.34, 11-18, 2021. (徳島大学機関リポジトリ) ● Metadata: 116287 (出版サイトへのリンク) ● Publication site (DOI): 10.20738/johb.34.1_11 (文献検索サイトへのリンク) ● CiNii @ 国立情報学研究所 (CRID): 1390570784697431168 ● Search Scopus @ Elsevier (DOI): 10.20738/johb.34.1_11 (徳島大学機関リポジトリ: 116287, DOI: 10.20738/johb.34.1_11, CiNii: 1390570784697431168)
8.	Tsendsuren Khurel-Ochir, Takashi Izawa, Akihiko Iwasa, Fumiya Kano, Akihito Yamamoto and Eiji Tanaka : The immunoregulatory role of p21 in the development of the temporomandibular joint-osteoarthritis., Clinical and Experimental Dental Research, Vol.7, No.3, 313-322, 2021. (要約) mice aged 8 weeks were divided into the untreated and treated groups. In the treated groups, mechanical stress was applied to the temporomandibular joint (TMJ) through forced mouth opening for 3 hr/day for 7 days. The dissected TMJs were assessed using micro-CT, histology, and immunohistochemistry. (徳島大学機関リポジトリ) ● Metadata: 116060 (出版サイトへのリンク) ● Publication site (DOI): 10.1002/cre2.404 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 33567474 ● Search Scopus @ Elsevier (PMID): 33567474 ● Search Scopus @ Elsevier (DOI): 10.1002/cre2.404 (徳島大学機関リポジトリ: 116060, DOI: 10.1002/cre2.404, PubMed: 33567474)
9.	Naoko Ogasawara, Fumiya Kano, Noboru Hashimoto, Hiroki Mori, YAO LIU, LINZE XIA, Takuma Sakamaki, Hideharu Hibi, Tsutomu Iwamoto, Eiji Tanaka and Akihito Yamamoto : Factors Secreted from Dental Pulp Stem Cells Show Multifaceted Benefits for Treating Experimental Temporomandibular Joint Osteoarthritis, Osteoarthritis and Cartilage, Vol.28, No.6, 831-841, 2020. (要約) Temporomandibular joint osteoarthritis (TMJOA) is a degenerative disease characterized by progressive cartilage degeneration, abnormal bone remodeling, and chronic pain. In this study, we aimed to investigate effective therapies to reverse or suppress TMJOA progression. To this end, we performed intravenous administration of serum free conditioned media from human exfoliated deciduous teeth stem cells (SHED-CM) into a mechanical-stress induced murine TMJOA model. SHED-CM administration markedly suppressed temporal muscle inflammation, and improved bone integrity and surface smoothness of the destroyed condylar cartilage. Moreover, SHED-CM treatment decreased the number of IL-1β, iNOS, and MMP-13 expressing chondrocytes, whereas it specifically increased PCNA-positive cells in the multipotent polymorphic cell layer. Notably, the numbers of TUNEL-positive apoptotic chondrocytes in the SHED-CM treated condyles were significantly lower than in those treated with DMEM, whereas the proteoglycan positive area was restored to a level similar to that of the sham treated group, demonstrating that SHED-CM treatment regenerated the mechanical-stress injured condylar cartilage and subchondral bone. Secretome analysis revealed that SHED-CM contained multiple therapeutic factors that act in osteochondral regeneration. Our data demonstrated that SHED-CM treatment promoted the regeneration and repair of mechanical-stress induced mouse TMJOA. Our observations suggest that SHED-CM has potential to be a potent tissue-regenerating therapeutic agent for patients with severe TMJOA. (徳島大学機関リポジトリ) ● Metadata: 115291 (出版サイトへのリンク) ● Publication site (DOI): 10.1016/j.joca.2020.03.010 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 32272195 ● Search Scopus @ Elsevier (PMID): 32272195 ● Search Scopus @ Elsevier (DOI): 10.1016/j.joca.2020.03.010 (徳島大学機関リポジトリ: 115291, DOI: 10.1016/j.joca.2020.03.010, PubMed: 32272195)
10.	K Okabe, R Kaneko, T Kawai, Fumiya Kano, Y Ohta and H Hibi : Oral self-injury associated with septicaemia in a case of Cornelia de Lange syndrome, Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology, Vol.32, No.2, 136-139, 2020. (出版サイトへのリンク) ● Publication site (DOI): 10.1016/j.ajoms.2019.10.003 (文献検索サイトへのリンク) ● Search Scopus @ Elsevier (DOI): 10.1016/j.ajoms.2019.10.003 (DOI: 10.1016/j.ajoms.2019.10.003)
11.	Keita Kawarabayashi, Fumiya Kano, Noboru Hashimoto, Hideharu Hibi, Tsutomu Iwamoto and Akihito Yamamoto : Conditioned Media from Human Dental Pulp Stem Cells Prevent Radiation-induced Skin Injury., Journal of Oral Health and Biosciences, Vol.33, No.1, 1-7, 2020. (徳島大学機関リポジトリ) ● Metadata: 114712 (出版サイトへのリンク) ● Publication site (DOI): 10.20738/johb.33.1_1 (文献検索サイトへのリンク) ● CiNii @ 国立情報学研究所 (CRID): 1390848250116869120 ● Search Scopus @ Elsevier (DOI): 10.20738/johb.33.1_1 (徳島大学機関リポジトリ: 114712, DOI: 10.20738/johb.33.1_1, CiNii: 1390848250116869120)
12.	Jun Ishikawa, Fumiya Kano, Yuji Ando, Hideharu Hibi and Akihito Yamamoto : Monocyte chemoattractant protein-1 and secreted ectodomain of sialic acid-binding Ig-like lectin-9 enhance bone regeneration by inducing M2 macrophages, Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology, Vol.31, No.3, 169-174, 2019. (出版サイトへのリンク) ● Publication site (DOI): 10.1016/j.ajoms.2018.12.007 (文献検索サイトへのリンク) ● Summary page in Scopus @ Elsevier: 2-s2.0-85059091442 (DOI: 10.1016/j.ajoms.2018.12.007, Elsevier: Scopus)
13.	Fumiya Kano, Norihisa Ichimura, Yukiko Wakayama, Kazuto Okabe, Hiroki Sakakura and Hideharu Hibi : Third molar pericoronitis in neutropenia, IDCases, Vol.13, e00419, 2018. (要約) We report the case of a 40 year-old woman who presented third molar pericoronitis in neutropenia. she had undergone extraction of the right third mandibular molar. This may have been due to an infection in the extraction socket or part of the crown. There was no inflammation seen after transplant of umbilical cord blood. (出版サイトへのリンク) ● Publication site (DOI): 10.1016/j.idcr.2018.e00419 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 30101065 ● Summary page in Scopus @ Elsevier: 2-s2.0-85049886658 (DOI: 10.1016/j.idcr.2018.e00419, PubMed: 30101065, Elsevier: Scopus)
14.	Y Nakao, T Tanigawa, Fumiya Kano, H Tanaka, N Katahira, T Ogawa, K Murotani, T Nagata and R Shibata : Diagnostic role of mean platelet volume in tonsillitis with and without peritonsillar abscess, The Journal of Laryngology and Otology, Vol.132, No.7, 615-618, 2018. (要約) To assess the diagnostic role of mean platelet volume in tonsillitis with and without peritonsillar abscess. Mean platelet volume and other laboratory data were retrospectively investigated. Mean platelet volume was significantly lower in the tonsillitis group (7.8 per cent ± 0.7 per cent) than in the control group (8.7 per cent ± 0.6 per cent; p < 0.0001), and it was significantly lower in the abscess group (7.5 per cent ± 0.6 per cent) than in the no abscess group (8.0 per cent ± 0.7 per cent; p = 0.0277). White blood cell counts and C-reactive protein levels were not significantly different between patients with an abscess and those without. The mean platelet volume cut-off values for the diagnosis of tonsillitis and peritonsillar abscess were 7.95 fl and 7.75 fl, respectively. Our results suggest that a decreased mean platelet volume is associated with the development and severity of tonsillitis. This finding provides useful diagnostic information for physicians treating patients with tonsillitis. (キーワード) Adult / Case-Control Studies / Female / Humans / Male / Mean Platelet Volume / Middle Aged / Peritonsillar Abscess / Reference Values / Retrospective Studies / Severity of Illness Index / Tonsillitis (出版サイトへのリンク) ● Publication site (DOI): 10.1017/S0022215118000658 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 29888695 ● Search Scopus @ Elsevier (PMID): 29888695 ● Search Scopus @ Elsevier (DOI): 10.1017/S0022215118000658 (DOI: 10.1017/S0022215118000658, PubMed: 29888695)
15.	市村典久, 山本憲幸, 西川雅也, 山口聡, 加納史也, 日比英晴 : 顎下腺に発生したびまん性大細胞型B細胞リンパ腫を含むMALTリンパ腫の1例., 日本口腔外科学会雑誌, Vol.64, No.8, 470-474, 2018年. (出版サイトへのリンク) ● Publication site (DOI): 10.5794/jjoms.64.470 (文献検索サイトへのリンク) ● CiNii @ 国立情報学研究所 (CRID): 1390282763059796352 ● Search Scopus @ Elsevier (DOI): 10.5794/jjoms.64.470 (DOI: 10.5794/jjoms.64.470, CiNii: 1390282763059796352)
16.	T Tohru, T Hirokazu, Fumiya Kano, U Hiromi and I Shigeru : Nasal hemangiopericytoma successfully treated with a combination of rIL-2 and extranasal approaches, Journal of Surgical Case Reports, Vol.10, No.10, 1-3, 2017. (要約) Hemangiopericytomas (HPCs) are uncommon vascular tumors originating from extracapillary cells called pericytes, and rarely occur in the nose or paranasal sinuses. We treated a 57-year-old man with nasal HPC who presented with nasal obstruction and hemorrhage. Nasal endoscopy showed a readily bleeding mass between the right nasal septum and inferior turbinate. Enhanced CT revealed a heterogeneous mass lesion with an enhancement effect that filled the right nasal cavity. A biopsy specimen was proved to exhibit a HPC histopathology. Recombinant interleukin-2 (rIL-2) was administered with a measurement of natural killer cell (NK cell) activity. Afterwards, wide excision with an extranasal approach was performed. The use of rIL-2 caused not only increased NK cell activity but also a reduction in the tumor size. With a combination of rIL-2 and wide excision with extranasal approaches, no local recurrence or metastasis has occurred over the last 4 years. (出版サイトへのリンク) ● Publication site (DOI): 10.1093/jscr/rjx202 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 29423144 ● Search Scopus @ Elsevier (PMID): 29423144 ● Search Scopus @ Elsevier (DOI): 10.1093/jscr/rjx202 (DOI: 10.1093/jscr/rjx202, PubMed: 29423144)
17.	H Yuichiro, T Tohru, S Rei, N Hiroshi, Fumiya Kano, Y Satoshi, M Kenta, O Takaki and U Hiromi : Efficacy of the red blood cell distribution width for predicting the prognosis of Bell palsy: a pilot study, Eur Arch Otorhinolaryngo, Vol.32, 1031-1034, 2017.
18.	Yuichiro Horibe, Tohru Tanigawa, Rei Shibata, Hiroshi Nonoyama, Fumiya Kano, Satoshi Yamaguchi, Kenta Murotani, Takaki Ogawa and Hiromi Ueda : Efficacy of the red blood cell distribution width for predicting the prognosis of Bell palsy: a pilot study., European Archives of Oto-Rhino-Laryngology, Vol.274, No.5, 2303-2306, 2017. (出版サイトへのリンク) ● Publication site (DOI): 10.1007/s00405-016-4445-z (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 28197706 ● Summary page in Scopus @ Elsevier: 2-s2.0-85012924014 (DOI: 10.1007/s00405-016-4445-z, PubMed: 28197706, Elsevier: Scopus)
19.	Fumiya Kano, Kohki Matsubara, Minoru Ueda, Hideharu Hibi and Akihito Yamamoto : Secreted Ectodomain of Sialic Acid-Binding Ig-Like Lectin-9 and Monocyte Chemoattractant Protein-1 Synergistically Regenerate Transected Rat Peripheral Nerves by Altering Macrophage Polarity, Stem Cells, Vol.35, No.3, 641-653, 2017. (要約) Peripheral nerves (PNs) exhibit remarkable self-repairing reparative activity after a simple crush or cut injury. However, the neuronal transection involving a nerve gap overwhelms their repairing activity and causes persistent paralysis. Here, we show that an implantation of the serum-free conditioned medium from stem cells from human exfoliated deciduous teeth (SHED-CM) immersed in a collagen sponge into the nerve gap formed by rat facial nerves transection restored the neurological function. In contrast, SHED-CM specifically depleted of a set of anti-inflammatory M2 macrophage inducers, monocyte chemoattractant protein-1 (MCP-1) and the secreted ectodomain of sialic acid-binding Ig-like lectin-9 (sSiglec-9) lost the ability to restore neurological function in this model. Notably, the combination of MCP-1 and sSiglec-9 induced the polarization of M2 macrophages in vitro, resulting in the expression of multiple trophic factors that enhanced proliferation, migration, and differentiation of Schwann cells, blood vessel formation, and nerve fiber extension. Furthermore, the implantation of a collagen graft containing MCP-1/sSiglec-9 into the nerve gap induced anti-inflammatory M2 macrophage polarization, generated a Schwann-cell bridge instead of fibrotic scar, induced axonal regrowth, and restored nerve function. The specific elimination of M2 macrophages by Mannosylated-Clodrosome suppressed the MCP-1/sSiglec-9-mediated neurological recovery. Taken together, our data suggest that MCP-1/sSiglec-9 regenerates PNs by inducing tissue-repairing M2 macrophages and may provide therapeutic benefits for severe peripheral nerve injuries. Stem Cells 2017;35:641-653. (キーワード) Animals / Cell Differentiation / Cell Movement / Cell Polarity / Cell Proliferation / Chemokine CCL2 / Child / Facial Nerve / Female / Ganglia, Spinal / Humans / Inflammation / Macrophages / Nerve Regeneration / Neuronal Outgrowth / Peripheral Nerves / Rats, Sprague-Dawley / Recovery of Function / Schwann Cells / Sialic Acid Binding Immunoglobulin-like Lectins / Signal Transduction / Stem Cells / Tooth, Deciduous (出版サイトへのリンク) ● Publication site (DOI): 10.1002/stem.2534 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 27862629 ● Search Scopus @ Elsevier (PMID): 27862629 ● Search Scopus @ Elsevier (DOI): 10.1002/stem.2534 (DOI: 10.1002/stem.2534, PubMed: 27862629)
20.	T Tohru, Fumiya Kano, I Daisuke and K Tessei : Adult retropharyngeal abscess., IDCases, Vol.10, 130-131, 2017. (出版サイトへのリンク) ● Publication site (DOI): 10.1016/j.idcr.2017.11.001 (文献検索サイトへのリンク) ● Summary page in Scopus @ Elsevier: 2-s2.0-85033373567 (DOI: 10.1016/j.idcr.2017.11.001, Elsevier: Scopus)
21.	Kohki Matsubara, Yoshihiro Matsushita, Kiyoshi Sakai, Fumiya Kano, Megumi Kondo, Mariko Noda, Noboru Hashimoto, Shiro Imagama, Naoki Ishiguro, Akio Suzumura, Minoru Ueda, Koichi Furukawa and Akihito Yamamoto : Secreted ectodomain of sialic acid-binding Ig-like lectin-9 and monocyte chemoattractant protein-1 promote recovery after rat spinal cord injury by altering macrophage polarity., The Journal of Neuroscience, Vol.35, No.6, 2452-2464, 2015. (要約) Engrafted mesenchymal stem cells from human deciduous dental pulp (SHEDs) support recovery from neural insults via paracrine mechanisms that are poorly understood. Here we show that the conditioned serum-free medium (CM) from SHEDs, administered intrathecally into rat injured spinal cord during the acute postinjury period, caused remarkable functional recovery. The ability of SHED-CM to induce recovery was associated with an immunoregulatory activity that induced anti-inflammatory M2-like macrophages. Secretome analysis of the SHED-CM revealed a previously unrecognized set of inducers for anti-inflammatory M2-like macrophages: monocyte chemoattractant protein-1 (MCP-1) and the secreted ectodomain of sialic acid-binding Ig-like lectin-9 (ED-Siglec-9). Depleting MCP-1 and ED-Siglec-9 from the SHED-CM prominently reduced its ability to induce M2-like macrophages and to promote functional recovery after spinal cord injury (SCI). The combination of MCP-1 and ED-Siglec-9 synergistically promoted the M2-like differentiation of bone marrow-derived macrophages in vitro, and this effect was abolished by a selective antagonist for CC chemokine receptor 2 (CCR2) or by the genetic knock-out of CCR2. Furthermore, MCP-1 and ED-Siglec-9 administration into the injured spinal cord induced M2-like macrophages and led to a marked recovery of hindlimb locomotor function after SCI. The inhibition of this M2 induction through the inactivation of CCR2 function abolished the therapeutic effects of both SHED-CM and MCP-1/ED-Siglec-9. Macrophages activated by MCP-1 and ED-Siglec-9 extended neurite and suppressed apoptosis of primary cerebellar granule neurons against the neurotoxic effects of chondroitin sulfate proteoglycans. Our data suggest that the unique combination of MCP-1 and ED-Siglec-9 repairs the SCI through anti-inflammatory M2-like macrophage induction. (キーワード) Animals / Antigens, CD / 血液脳関門 (blood-brain barrier) / Brain Injuries / Cell Polarity / 小脳 (cerebellum) / Chemokine CCL2 / Child / Culture Media, Conditioned / Cytokines / Dental Pulp / Humans / Macrophages / Mice / Mice, Inbred C57BL / Rats / Rats, Sprague-Dawley / Receptors, CCR2 / Sialic Acid Binding Immunoglobulin-like Lectins / Spinal Cord Injuries / Tooth, Deciduous (出版サイトへのリンク) ● Publication site (DOI): 10.1523/JNEUROSCI.4088-14.2015 (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 25673840 ● Summary page in Scopus @ Elsevier: 2-s2.0-84922553212 (DOI: 10.1523/JNEUROSCI.4088-14.2015, PubMed: 25673840, Elsevier: Scopus)
22.	Fumiya Kano, Kohki Matsubara and Akihito Yamamoto : The development of new therapy facial nerve injury using the m2 macrophage induction factors, Inflammation Research, Vol.64, No.Sup2, S229-S230, 2015.

総説・解説:

1.	Eiji Tanaka, YAO LIU, LINZE XIA, Naoko Ogasawara, Takuma Sakamaki, Fumiya Kano, Noboru Hashimoto, Xingmei Feng and Akihito Yamamoto : Effectiveness of low-intensity pulsed ultrasound on osteoarthritis of the temporomandibular joint: A review., Annals of Biomedical Engineering, Vol.48, No.8, 2158-2170, Jun. 2020. (要約) Loading is indispensable for the growth, development, and maintenance of joint tissues, including mandibular condylar cartilage, but excessive loading or reduced host adaptive capacity can considerably damage the temporomandibular joint (TMJ), leading to temporomandibular joint osteoarthritis (TMJ-OA). TMJ-OA, associated with other pathological conditions and aging processes, is a highly degenerative disease affecting the articular cartilage. Many treatment modalities for TMJ-OA have been developed. Traditional clinical treatment includes mainly nonsurgical options, such as occlusal splints. However, non-invasive therapy does not achieve joint tissue repair and regeneration. Growing evidence suggests that low-intensity pulsed ultrasound (LIPUS) accelerates bone fracture healing and regeneration, as well as having extraordinary effects in terms of soft tissue repair and regeneration. The latter have received much attention, and various studies have been performed to evaluate the potential role of LIPUS in tissue regeneration including that applied to articular cartilage. The present article provides an overview of the status of LIPUS stimulation used to prevent the onset and progression of TMJ-OA and enhance the tissue regeneration of mandibular condylar cartilage. The etiology and management of TMJ-OA are explained briefly, animal models of TMJ-OA are described, and the effectiveness of LIPUS on cell metabolism and tissue regeneration in the TMJ is discussed. (出版サイトへのリンク) ● Publication site (DOI): 10.1007/s10439-020-02540-x (文献検索サイトへのリンク) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 32514932 ● Search Scopus @ Elsevier (PMID): 32514932 ● Search Scopus @ Elsevier (DOI): 10.1007/s10439-020-02540-x (DOI: 10.1007/s10439-020-02540-x, PubMed: 32514932)
2.	Akihito Yamamoto, S Kiyoshi, M Kohki, Fumiya Kano and U Minoru : Multifaceted neuro-regenerative activities of human dental pulp stem cells for functional recovery after spinal cord injury., Neuroscience Research, Vol.78, 16-20, 2014.

国際会議:

1.	Fumiya Kano : Factors secreted from dental pulp stem cells show multifaceted benefits for Synergistically Regenerate Transected Rat Peripheral Nerves by Altering Macrophage Polarity., 第68回国際歯科研究学会日本部会総会・学術大会, Nov. 2020.
2.	Fumiya Kano, M Kohki, U Minoru, H Hideharu and Akihito Yamamoto : Secreted Ectodomain of Sialic Acid-Binding Ig-Like Lectin-9 and Monocyte Chemoattractant Protein-1 Synergistically Regenerate Transected Rat Peripheral Nerves by Altering Macrophage Polarity., 13th World Congress on Inflammation., London, Jul. 2017.
3.	Fumiya Kano, M Kohki, U Minoru, H Hideharu and Akihito Yamamoto : SECRETED ECTODOMAIN OF SIALIC ACID-BINDING IMMUNOGLOBULIN-LIKE LECTIN-9 AND MONOCYTE CHEMOATTRACTANT PROTEIN-1 DERIVED FROM DENTAL PULP STEM CELLS SYNERGISTICALLY REGENERATE TRANSECTED RAT PERIPHERAL NERVES BY ALTERING MACROPHAGE POLARITY., The 23th International Conference on Oral and Maxillofacial Surgery., Hong Kong, Mar. 2017.
4.	Fumiya Kano, M Kohki and Akihito Yamamoto : THE DEVELOPMENT OF NEW THERAPY FACIAL NERVE INJURY USING THE M2 MACROPHAGE INDUCTION FACTORS., The 22nd International Conference on Oral and Maxillofacial Surgery., Melbourne, Oct. 2015.
5.	Fumiya Kano, M Kohki and Akihito Yamamoto : THE DEVELOPMENT OF NEW THERAPY FACIAL NERVE INJURY USING THE M2 MACROPHAGE INDUCTION FACTORS., 12th World Congress on Inflammation, Boston, Aug. 2015.
6.	Fumiya Kano, M Kohki, Akihito Yamamoto and U Minoru : THE DEVELOPMENT OF NEW THERAPY FACIAL NERVE INJURY USING THE M2 MACROPHAGE INDUCTION FACTORS., AAOMS 96th Annual Meeting, Hawaii, Sep. 2014.

国内講演発表:

1.	Cheng Ding, Noboru Hashimoto, Fumiya Kano, LINZE XIA, Yang Xu and Akihito Yamamoto : Soluble Siglec-9 attenuated the joint destruction in Collagen Antibody Induced Arthritis mouse model, 第22回日本再生医療学会総会抄録, 168, Mar. 2023.
2.	沖若奈, 加納史也, 西原嵩晃, 橋本登, 山本朗仁 : 放射線唾液腺障害に対する歯髄幹細胞由来上清の治療効果の検討, 第64回歯科基礎医学会学術大会, 2022年9月. (キーワード) 歯髄幹細胞 / 放射線性口腔乾燥 / 培養上清
3.	猿山善章, 森岡莉彩, 加納史也, 橋本登, 山本朗仁 : 分泌型シアル酸認識レクチンを用いた関節リウマチの新規治療法の開発, 第76回NPO法人日本口腔科学会学術集会, 2022年4月. (キーワード) シアル酸認識レクチン / 関節リウマチ
4.	沖若奈, 加納史也, 西原嵩晃, 橋本登, 山本朗仁 : ⻭髄幹細胞培養上清の抗酸化効果による放射線性⼝腔乾燥症の治療メカニズム, 第76回NPO法人日本口腔科学会学術集会, 2022年4月. (キーワード) 歯髄幹細胞 / 培養上清 / 口腔乾燥
5.	森岡莉彩, 猿山善章, 加納史也, 橋本登, 山本朗仁 : 分泌型シアル酸認識レクチン-9とケモカインMCP-1 を用いた関節リウマチの新規治療法の開発, 四国歯学会第59回例会, 2022年3月. (キーワード) シアル酸認識レクチン-9 / MCP-1 / 関節リウマチ
6.	Waskitho Arief, Yumiko Yamamoto, Raman Swarna Lakshmi, Fumiya Kano, Huijiao Yan, Kazuo Okura, Daisuke Ikutame, Masamitsu Ohshima, Otto Baba, Akihito Yamamoto and Yoshizo Matsuka : Bilateral botulinum toxin type A effect on orofacial neuropathic pain of animal model, 徳島大学脳科学クラスターミニリトリート, Feb. 2022.
7.	LINZE XIA, Fumiya Kano, Noboru Hashimoto and Akihito Yamamoto : Conditioned Medium from the Stem Cells of Human Exfoliated Deciduous Teeth Ameliorates Experimental Temporomandibular Joint Osteoarthritis by Inducing M2 Phenotype of Macrophages, 蔵本免疫懇話会, Nov. 2021. (キーワード) 培養上清 / 脱落乳歯歯髄幹細胞 / 変形性顎関節症 / M2マクロファージ
8.	加納史也 : 歯髄幹細胞培養上清の抗酸化効果による放射線性口腔乾燥症の治療メカニズム, 蔵本免疫懇話会, 2021年11月. (キーワード) 歯髄幹細胞 / 培養上清 / 酸化ストレス (oxidative stress) / 口腔乾燥
9.	坂巻拓馬, 岩浅亮彦, 夏霖泽, Yao Liu, 加納史也, 山本朗仁, 田中栄二 : 変形性顎関節症に対する低出力超音波パルスの治療効果, 日本矯正歯科学会雑誌, 2021年11月.
10.	加納史也, LIU YAO, 橋本登, 松香芳三, 田中栄二, 山本朗仁 : ⻭髄幹細胞由来無⾎清培養上清は坐⾻神経結紮モデルマウスの神経障害性疼痛を改善する, 第63回歯科基礎医学会学術大会, 2021年9月. (キーワード) 歯髄幹細胞 / 培養上清 / 神経障害性疼痛
11.	西原嵩晃, 沖若奈, 加納史也, 橋本登, 河原林啓太, 山本朗仁 : 放射線唾液腺障害に対する歯髄幹細胞由来上清の治療効果の検討, 四国歯学会第57回例会, 2021年3月. (キーワード) 歯髄幹細胞 / 培養上清 / 口腔乾燥
12.	夏霖泽, 加納史也, 橋本登, 小笠原直子, LIU YAO, 田中栄二, 山本朗仁 : :Analysis of the Therapeutic Mechanisms of SHED-CM for Experimentally Induced Temporomandibular Joint Osteoarthritis in Mice., 四国歯学会雑誌, 2021年3月.
13.	加納史也, 小笠原直子, 橋本登, 森浩喜, 宮嵜彩, 岩本勉, 田中栄二, 山本朗仁 : 歯髄幹細胞由来無血清培養上清を用いた変形性顎関節症の治療法開発, 第62回歯科基礎医学会学術大会, 2020年9月. (キーワード) 変形性顎関節症 / 乳歯歯髄幹細胞 / 乳歯歯髄幹細胞由来培養上清
14.	橋本登, 加納史也, 河原林啓太, LIU YAO, 夏霖泽, 山本朗仁 : ヒト乳歯歯髄幹細胞由来培養液における皮膚炎モデルマウス治療効果因子のプロテオーム解析, 第41回日本炎症・再生医学会, 2020年7月.
15.	加納史也, LIU YAO, 橋本登, 松香芳三, 田中栄二, 山本朗仁 : 歯髄幹細胞由来無血清培養上清は坐骨神経結紮モデルマウスの神経障害性疼痛を改善する, 日本炎症・再生医学会, 2020年7月.
16.	橋本登, 加納史也, 河原林啓太, LIU YAO, 山本朗仁 : ヒト乳歯歯髄幹細胞由来培養液における皮膚炎モデルマウス治療効果因子のプロテオーム解析, 第19回日本再生医療学会総会, 2020年5月.
17.	加納史也, 小笠原直子, 橋本登, 森浩喜, 宮嵜彩, 岩本勉, 田中栄二, 山本朗仁 : 歯髄幹細胞由来無血清培養上清を用いた変形性顎関節症の治療法開発, 第19回日本再生医療学会, 20, 2020年3月.
18.	後野秀一朗, 加納史也, 有馬秀貴, 橋本登, 寺町順平, 岩本勉, 山本朗仁 : 歯髄幹細胞由来無血清培養上清を用いた脊髄損傷の治療法開発, 徳島県歯科医学大会, 37, 2020年2月.
19.	有馬秀貴, 加納史也, 後野秀一朗, 橋本登, 寺町順平, 岩本勉, 山本朗仁 : 間葉系幹細胞由来分泌因子がSchwann細胞の活性化に与える影響, 徳島県歯科医学大会, 36, 2020年2月.
20.	河原林啓太, 加納史也, 橋本登, 寺町順平, 青田桂子, 東雅之, 岩本勉, 山本朗仁 : 歯髄幹細胞由来無血清培養上清を用いた口腔乾燥症の治療法の開発, 徳島県歯科医学大会, 20, 2020年2月.
21.	小笠原直子, 加納史也, 橋本登, LIU YAO, 森浩喜, 寺町順平, 岩本勉, 田中栄二, 山本朗仁 : 歯髄幹細胞由来無血清培養上清を用いた変形性顎関節症の治療法開発, 徳島県歯科医学大会, 20, 2020年2月.
22.	加納史也, 神尾尚伸, 鶴田剛士, 日比英晴 : 抜歯後に長期間疼痛が継続した，筋・筋膜痛による関連痛の1例, 第64回公益社団法人日本口腔外科学会総会・学術大会, 2019年11月.
23.	加納史也, 神尾尚伸, 鶴田剛士, 日比英晴, 山本朗仁 : 抜歯後に長期間疼痛が継続した，筋・筋膜痛による関連痛の1例, 第24回日本口腔顔面痛学会学術大会, 2019年9月.
24.	加納史也, 西須大徳, 神尾尚伸, 鶴田剛士, 坂口晃平, 日比英晴, 山本朗仁 : 歯冠修復後に進行した歯髄炎による対顎歯への関連痛の1例, 第24回日本口腔顔面痛学会学術大会, 2019年9月.
25.	加納史也, 西須大徳, 神尾尚伸, 鶴田剛士, 坂口晃平, 日比英晴, 山本朗仁 : 歯冠修復後に進行した歯髄炎による対顎歯への関連痛の1例, 第29 回日本口腔内科学会, 2019年9月.

その他・研究会:

1.	西田真衣, 夏霖泽, Khurel-Ochir Tsendsuren, 加納史也, 田中栄二, 山本朗仁 : The therapeutic effect of soluble sialic acid-recognizing immunoglobulin-like lectin 9 on the temporomandibular joint arthritis, 2023年度骨・筋とCaクラスター・ミニリトリート, 2024年2月.
2.	加納史也, 橋本登, 山本朗仁 : ⻭髄幹細胞培養上清の抗酸化効果による放射線性⼝腔乾燥症の治療メカニズム, 四国免疫フォーラム, 2023年6月. (キーワード) 歯髄幹細胞 / 放射線性口腔乾燥症 / 培養上清
3.	LINZE XIA, Fumiya Kano, Noboru Hashimoto, Eiji Tanaka and Akihito Yamamoto : Conditioned Medium from M2 Macrophages Alleviates Murine Temporomandibular Joint Osteoarthritis, 第22回日本再生医療学会総会抄録, 73, Mar. 2023.

特許:

1.	山本朗仁, 加納史也, 橋本登, 高橋伸典 : 骨疾患を処置または予防するための組成物, 特願P275144 (2021年9月), .

科学研究費補助金 (KAKEN Grants Database @ NII.ac.jp)

時空間的遺伝子発現解析による関節再生メカニズムの検証 (研究課題/領域番号: 24K02646 )
シングルセル解析を用いた放射線性唾液腺障害の回復メカニズムの解明 (研究課題/領域番号: 23K15978 )
可溶性レクチンを用いた関節リウマチ病態制御機構の検討 (研究課題/領域番号: 23K06414 )
分泌型シアル酸認識レクチンによる関節再生メカニズムの解析 (研究課題/領域番号: 21H03055 )
乳歯歯髄幹細胞培養上清由来因子を用いた新規皮膚炎治療法の検討 (研究課題/領域番号: 20K08690 )
ミクログリア由来エクソソームによる神経障害性疼痛のメカニズム解明 (研究課題/領域番号: 19K18241 )
ミクログリア制御による新規疼痛制御治療薬の開発 (研究課題/領域番号: 17H06757 )
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助教 : 加納史也