国立研究開発法人 国立成育医療研究センター National Center for Child Health and Development

代表: 03-3416-0181 / 予約センター(病院): 03-5494-7300
〈月~金曜日(祝祭日を除く)9時〜17時〉

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研究者・企業の方へ Scholar & Enterprise

研究者・企業の方へ Scholar & Enterprise

RI管理室

研究室紹介

ラジオアイソト−プ施設の維持管理・安全対策、ラジオアイソト−プ使用に関する変更・許可等の届け出・申請、使用者の健康管理、そして安全に使用するための指導及び知識の周知教育、ラジオアイソト−プ関連の情報提供や研究活動などを支援しています。
研究活動においては、様々な臓器移植、自己免疫疾患モデル、或はIn vitroの評価系を用いて、免疫寛容の誘導・維持に関与する分子・細胞の機序の解明およびCell Based Therapy を中心に、制御性T細胞、iPS細胞由来制御性樹状細胞(DC)、ミエロイド由来抑制細胞(MDSC)、間葉系幹細胞を用いる免疫制御細胞療法の確立するための基礎研究を行っています。また、新規免疫抑制剤、新規臓器保存法の開発を積極的に進めています。近い将来、これらの成果を移植医療・再生医療への応用を通じて、移植後患者のQOLの向上、医療費の削減に繋げていきたいと考えています。

研究内容

  1. 安全かつ効果的にドナー造血幹細胞移植後キメリズム構築することで、特異的臓器移植免疫寛容の誘導を目標として目指しています。
  2. iPS細胞から制御性樹状細胞、ミエロイド由来抑制細胞への分化誘導を行い、免疫制御細胞療法を確立することを目指しています。
  3. 移植免疫寛容の誘導・維持に関与する分子・細胞の機序の解明を行い、その成果を踏まえ、新規化合物の免疫抑制剤の開発を進めています。
  4. 水素分子を医療の現場で安全かつ安定に使用できる「非破壊的水素含有装置」を用い、その効果を検証し、近い将来の臨床応用を目指しています。

スタッフ

RI管理室

室員

  • 胡 鑫(研究員)

業績

2021

1.    Hu X, Que WT, Hirano H, Wang ZD, Nozawa N, Ishii T, Ishizuka M, Ito H, Takahashi K, Nakajima M, Tanaka T, Zhu P, Guo WZ, Li Xiao K*. 5-ALA/SFC enhanced the antitumor effects of PD-L1 blockade via regulated exhaustion T cell metabolism in melanoma model. Cancer Science May 2. 2021. doi: 10.1111/cas.14930.

2.    Liu C, Wang ZD, Hu X, Ito H, Takahashi K, Nakajima M, Tanaka T, Zhu P, Li Xiao K*. 5-aminolevulinic acid combined with sodium ferrous citrate ameliorated lupus nephritis in a mouse chronic graft-versus-host disease model. Int Immunopharmacol 96:107626; 2021.

3.    Zheng QY, Zhang SJ, Wen-Zhi Guo WZ, Li Xiao K*. The unique immunomodulatory properties of MSC-derived exosomes in organ transplantation. Frontiers in Immunology 12: 659621; 2021.

4.    Hirano S, Aoki Y, Kurokawa R, Li Xiao K, Ichimaru N, Takahara S, Takefuji Y. Protective effects of hydrogen gas inhalation on radiation-induced bone marrow damage in cancer patients: a retrospective observational study. Medical Gas Research 11(3):104-109; 2021.

5.    Li SW, Takahara T, Que WT, Fujino M, Guo WZ, Hirano S, Ye LP, Li Xiao K*. Hydrogen-rich water protects liver injury in nonalcoholic steatohepatitis though HO-1 enhancement via IL-10 and Sirt 1 signaling. Am J Physiol Gastrointestinal and Liver Physiol 320(4): G450-463; 2021.

6.    Que WT, Li Xiao K*. Regulatory T Cells for the Induction of Transplantation Tolerance. In: SG-Zheng editor. Chapter 15: T Regulatory Cells in Human Health and Diseases. Springer Publishers Inc., pp.289-302, 2021.

7.    Zhao J, Que WT, Du XX, Fujino M, Ichimaru N, Ueta H, Tokuda N, Guo WZ, Zabrocki P, Haard HD, Nonomura N, Li Xiao K*. Monotherapy with anti-CD70 antibody causes long-term mouse cardiac allograft acceptance with induction of tolerogenic dendritic cells. Frontiers in Immunology 11:555996; 2021.

8.    Matsuda Y, Hiramitsu T, Li Xiao K, Watanabe T. Characteristics of immunoglobulin M type antibodies of different origins from the immunologic and clinical viewpoints and their application in controlling antibody-mediated allograft rejection. Pathogens 10(1), 4;2021.

2020

1.    Wang ZD, Ma K, Liu C, Hu X, Que WT, Ito H, Takahashi K, Nakajima M, Tanaka T, Ren K, Guo WZ, Yi SQ, Li Xiao K*. 5-Aminolevulinic acid combined with sodium ferrous ameliorated liver injury in a murine acute graft-versus- host disease model by reducing inflammation responses through PGC-1α activation. Drug Discoveries & Therapeutics 14(6):304-312; 2020.

2.    Que WT, Guo WZ, Li Xiao K*. Manipulation of regulatory dendritic cells for induction transplantation tolerance. Frontiers in Immunology 11:582658; 2020.

3.    Que WT, Hu X, Fujino M, Terayama H, Sakabe K, Fukunishi N, Zhu P, Yi SQ, Yamada Y, Zhong L, Li Xiao K*. Prolonged cold ischemia time in mouse heart transplantation using supercooling preservation. Transplantation 104(9): 1879-1889; 2020.

4.    Jiang YZ, Que WT, Zhu P, Li Xiao K*. The role of diverse liver cells in liver transplantation tolerance. Frontiers in Immunology 11:1203; 2020.

5.    Sheng C, Li Xiao K*. The Role of Immune Modulation in Pathogenesis of IgA Nephropathy. Frontiers in Medicine 7:92; 2020.

6.    Dai Y, Yi K, Shimada K, Ren K, Wang Z, Terayama H, Li Xiao K, Yi SQ. Anatomy of the coronary arteries in fetal pigs: comparison with human anatomy. Anat Sci Int. 95(2): 265-276; 2020.

7.    Wang PP, Zhao MY, Chen ZH, Wu GJ, Fujino M, Chen Zhang C, Zhou WJ, Zhao MW, Hirano S, Li Xiao K*, Zhao LL. Hydrogen gas attenuates hypoxic-ischemic brain injury via regulation of the MAPK/ HO-1/PGC-1α pathway in neonatal rats. Oxid Med Cell Longev 2020:6978784; 2020.

8.    Wang J, Liu C, Que W, Fujino M, Tong G, Yan H, Li Xiao K*. Immunomodulatory effects of Salvianolic acid B in a spontaneous abortion mouse model. J Reprod Immunol. 137:103075. 2020.

2019

1.     Liu C, Fujino M, Zhu S, Isaka Y, Ito H, Takahashi K, Nakajima M, Tanaka T, Zhu P, Li Xiao K*. 5-ALA/SFC enhances HO-1 expression through the MAPK/Nrf2 antioxidant pathway and attenuates murine tubular epithelial cell apoptosis. FEBS Open Bio. 9(11): 1928-1938; 2019.

2.     Liu C, Zhu P, Fujino M, Zhu S, Ito H, Takahashi K, Nakajima M, Tanaka T, Zhuang J, Li Xiao K*. 5-ALA/SFC attenuated binge alcohol-induced gut leakiness and inflammatory liver disease in HIV transgenic rats. Alcohol Clin Exp Res. 43(8): 1651-1661; 2019.

3.     Liu NB, Wu M, Chen C, Fujino M, Huang JS, Zhu P, Li Xiao K*. Novel Molecular Targets Participating in Myocardial Ischemia-Reperfusion Injury and Cardioprotection. Cardiol Res Pract. 2019:6935147; 2019.

4.     Wang J, Liu C, Fujino M, Tong G, Zhang Q, Li Xiao K*, Yan H. Stem cells as a resource for treatment infertility-related diseases. Curr Mol Med. 19(8): 539-546; 2019.

5.     Wu G, Chen Z, Wang P, Zhao M, Fujino M, Zhang C, Zhou W, Hirano SI, Li Xiao K, Zhao L. Hydrogen inhalation protects hypoxic-ischemic brain damage by attenuating inflammation and apoptosis in neonatal rats. Exp Biol Med. 244(12): 1017-1027; 2019.

6.     Zhao J, Yang XC, Fujino M, Ichimura N, Que WT, Li Xiao K*, Takahara S. Salvianolic acid B ameliorates liver injury in a murine aGvHD model by decreasing inflammatory responses via upregulation of HO-1. Transpl Immunol. 55: 101203; 2019.

7.     Toyama S, Migita O, Fujino M, Kunieda T, Kosuga M, Fukuhara Y, Nagahara Y, Li Xiao K*. Okuyama T. New treatment method for mucopolysaccharidosis type VI by liver transplantation. Pediatr Int. 261(2): 180-189; 2019.

8.     Wang Y, Zenkoh J, Gerelchuluun A, Sun L, Cai S, Li Xiao K, Tsuboi K. Administration of Dendritic Cells and Anti-PD-1 Antibody Converts X-ray Irradiated Tumors Into Effective In situ Vaccines. Int J Radiat Oncol Biol Phys. 103(4): 958-969; 2019.

9.     Uto K, Sakamoto S, Que WT, Shimata K, Hashimoto S, Sakisaka M, Narita Y, Daiki Y, Zhong L, Yoshihiro K, Kurokawa R, Li Xiao K, Inomata Y, Hibi T. Hydrogen rich solution attenuates cold ischemia-reperfusion injury in rat liver transplantation. BMC Gastroenterol. 19(1): 25; 2019.

10.  Liu C, Zhu P, Fujino M, Isaka Y, Ito H, Takahashi K, Nakajima M, Tanaka T, Zhuang J, Li Xiao K*. 5-aminolaevulinic acid (ALA), enhances heme oxygenase (HO)-1 expression and attenuates tubulointerstitial fibrosis and renal apoptosis in chronic cyclosporine nephropathy. Biochem Biophys Res Commun. 508(2): 583-589; 2019.

2018

1.    Liu C, Yang X, Zhu P, Fujino M, Ito H, Takahashi K, Nakajima M, Tanaka T, Wang J, Zhuang J, Zou HJ, Li Xiao K*. Combination of 5-aminolaevulinic acid and iron prevents skin fibrosis in murine sclerodermatous grafts-versus-host disease. Experimental Dermatology (In press)

2.    Li S, Fujino M, Ichimaru N, Kurokawa R, Hirano S, Mou L, Takahara S, Takahara T, Li Xiao K*. Molecular hydrogen protects against ischemia-reperfusion injury in a mouse fatty liver model via regulating HO-1 and Sirt1 expression. Sci Rep. 8(1): 14019; 2018. 

3.    Li S, Fujino M, Takahara T, Li Xiao K*. Protective role of heme oxygenase-1 in fatty liver ischemia-reperfusion injury. Med Mol Morphol. 2018 Aug 31. 

4.    Zhao M, Yang M, Que W, Zhong L, Fujino MLi Xiao K. Myeloid heme oxygenase-1: a new therapeutic target in anti-inflammation. Front Biosci. 23:2001-2015; 2018.

5.    Ito H, Nishio Y, Hara T, Sugihara H, Tanaka T, Li Xiao K. Oral administration of 5-aminolevulinic acid induces heme oxygenase-1 expression in peripheral blood mononuclear cells of healthy human subjects in combination with ferrous iron. Eur J Pharmacol. 833: 25-33; 2018.

6.    Hatayama N, Hirai S, Naito M, Hayato Terayama, Araki J, Yokota H, Matsushita M, Li Xiao K, Itoh M. Preservation of rat limbs by hyperbaric carbon monoxide and oxygen. Sci Rep. 8(1): 6627; 2018.

7.    Joyce D, Fujino M, Morita M, Araki R, Fung J, Qian S, Lu L, Li Xiao K*. Induced pluripotent stem cells-derived myeloid-derived suppressor cells regulate the CD8+ T cell response. Stem Cell Res. 29:32-41; 2018.

8.    Cheng XY, Li SY, Mao CJ, Wang MX, Chen J, Wang F, Wang GH, Deng WB, Li Xiao K, Liu CF. Serum Response Factor Promotes Dopaminergic Neuron Survival via Activation of Beclin 1-Dependent Autophagy. Neuroscience 371:288-295; 2018.

9.    Zhou WC, Wang Y, Fujino M, Shi LM, Jin L, Li Xiao K*, Wang JC. A standardized fold change (SFC) method for microarray differential expression analysis used to reveal genes involved in acute rejection in murine allograft models. FEBS Open Bio 8(3): 481-490; 2018.

2017

1.     Li S, Takahara T, Fujino M, Fukuhara Y, Sugiyama T, Li Xiao K*, Takahara S. Astaxanthin prevents ischemia-reperfusion injury of the steatotic liver in mice. PLoS One. 12(11): e0187810; 2017.

2.     Yang X, Liu C, Fujino M, Yang J, Li Xiao K*, Zou HJ. A modified graft-versus-host-induced model for systemic sclerosis, with pulmonary fibrosis in Rag2-deficient mice. FEBS Open Bio 7(9): 1316-1327; 2017.

3.     Cai SJ, Hou JG, Fujino M, Zhang Q, Ichimaru N, Takahara S, Araki R, Lu L, Chen JM, Zhuang J, Zhu P, Li Xiao K*. iPSC-derived Regulatory Dendritic Cells Inhibit Allograft Rejection via Generating Alloantigen-specific Regulatory T Cells. Stem Cell Reports 8(5): 1174-1189; 2017.

4.     Yang XC, Fujino M, Cai SJ, Li SW, Liu, C, Li Xiao K*.  Genetic polymorphisms of cytotoxic T-lymphocyte antigen 4 in primary biliary cholangitis: a meta-analysis. Journal of Immunology Research 2017:5295164; 2017.

5.     Abe T, Yazawa K, Fujino M, Imamura R, Hatayama N, Kakuta Y, Tsutahara K, Okumi M, Ichimaru, Kaimori J, Isaka Y, Seki K, Takahara S, Li Xiao K*, Nonomura. N High-pressure carbon monoxide preserves rat kidney grafts from apoptosis and inflammation. Lab Invest 97(4): 468-477; 2017.