研究者詳細 - 寺井　崇二

論文 - 寺井　崇二

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A liver cirrhosis detection method using probabilistic ROI combination 査読

Y. Fujita, T. Goto, Y. Mitani, Y. Hamamoto, M. Segawa, S. Terai, I. Sakaida

Proceedings of 11th International Conference on Quality Control by Artificial Vision 81 - 85 2013年

超音波画像を用いた肝硬変識別の高精度化査読

林孝哉, 藤田悠介, 三谷芳弘, 浜本義彦, 瀬川誠, 寺井崇二, 坂井田功

電気学会論文誌C 133 ( 2 ) 289 - 296 2013年

A note of liver cirrhosis classification on M-mode ultrasound images by higher-order local auto-correlation features. 査読

K. Fujino, Yoshihiro Mitani, T. Hayashi, Yusuke Fujita, Yoshihiko Hamamoto, Makoto Segawa, Shuji Terai, Isao Sakaida

2013 International Conference on Soft Computing and Pattern Recognition, SoCPaR 2013, Hanoi, Vietnam, December 15-18, 2013 50 - 53 2013年

Liver Resident Stem Cell 査読

Christina M. Takiya, Bruno Diaz Paredes, Luiz Fernando Quintanilha de Mesquita, Grazielle Suhett Dias, Lanuza Alaby Pinheiro Faccioli, Taro Takami, Shuji Terai, Isao Sakaida, Regina Coeli dos Santos Goldenberg

Resident Stem Cells and Regenerative Therapy 177 - 203 2013年

骨髄細胞投与による酸化ストレス制御を介した肝発癌抑制メカニズムの解明

高見太郎, 寺井崇二, 前田雅喜, 坂井田功

日本消化器病学会雑誌 109 ( 臨増大会 ) A721 - A721 2012年9月

肝疾患に対する先端医療骨髄由来培養細胞を用いた肝臓修復再生療法の実現化準備ヒト幹細胞を用いた臨床指針を踏まえて

寺井崇二, 高見太郎, 坂井田功

日本消化器病学会雑誌 109 ( 臨増大会 ) A424 - A424 2012年9月

Advanced Therapies Using Autologous Bone Marrow Cells for Chronic Liver Disease 査読

Taro Takami, Shuji Terai, Isao Sakaida

DISCOVERY MEDICINE 14 ( 74 ) 7 - 12 2012年7月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：DISCOVERY MEDICINE

The radical treatment currently for decompensated liver cirrhosis is still liver transplantation. However, liver transplants are not widely performed worldwide and development of genuine regeneration therapy for liver cirrhosis is an urgent task. We have developed a novel murine model [the green fluorescent protein (GFP)/carbon tetrachloride (CCl4) model], and reported that infused GFP-positive bone marrow cells repopulated cirrhotic liver. Moreover, repopulated bone marrow cells ameliorated liver fibrosis through higher expression of matrix metalloproteinase-9, consistent with improved liver functions and better survival rate. Based on these findings, we started a clinical trial of autologous bone marrow cell infusion (ABMi) therapy for decompensated liver cirrhotic patients, and reported the efficacy and the safety of this approach. On the other hand, various other clinical studies for liver disease have been also reported, including hepatic administration of autologous CD34-positive cells induced by granulocyte colony-stimulating factor (G-CSF), portal vein administration of CD133-positive mononuclear cells, and administration of autologous bone marrow derived mesenchymal stem cells (MSCs). Effectiveness of these approaches has been shown in some patients. We provided here an overview of the current status of liver regeneration therapies including our results of the murine GFP/CCl4 model and ABMi therapy for liver cirrhosis and future prospects. [Discovery Medicine 14(74):7-12, July 2012]

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【肝硬変update より良き診療のために】肝硬変診療のトピックス自己骨髄細胞を用いた肝修復再生療法の現状

高見太郎, 寺井崇二, 坂井田功

Medicina 49 ( 7 ) 1238 - 1239 2012年7月

Effect of transcatheter arterial infusion chemotherapy using iodized oil and degradable starch microspheres for hepatocellular carcinoma 査読

Takahiro Yamasaki, Issei Saeki, Yohei Harima, Junichi Zaitsu, Masaki Maeda, Haruko Tanimoto, Takuya Iwamoto, Isao Hidaka, Yohei Urata, Tsuyoshi Ishikawa, Taro Takami, Yuhki Yamaguchi, Koichi Uchida, Shuji Terai, Isao Sakaida

JOURNAL OF GASTROENTEROLOGY 47 ( 6 ) 715 - 722 2012年6月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：SPRINGER TOKYO

Transcatheter arterial infusion chemotherapy (TAI) using a combination of iodized oil (lipiodol) and degradable starch microspheres (DSMs) has been reported to be superior to TAI with either lipiodol or DSMs separately for the treatment of hepatocellular carcinoma (HCC), based on the results of a prospective randomized study. In the study reported here, we investigated the predictors influencing response and survival in HCC patients receiving TAI using lipiodol and DSMs.
A total of 50 HCC patients [Child-Pugh A/B, 34/16 patients; maximum tumor size 2.9 cm (mean); tumor number < 5/a parts per thousand yen5 = 29/21 patients] were administered a mixture of cisplatin and lipiodol, followed by the injection of DSMs.
According to the criteria of the Liver Cancer Study Group of Japan, the response [complete response (CR) + partial response (PR)] rate and CR rate were 72 and 38%, respectively [CR, 19 patients; PR, 17; stable disease, 9; progressive disease, 5]. The 1-, 2-, 3-, and 4-year cumulative survival rates were 85, 67, 41, and 35%, respectively, and the median survival time was 32.6 months. Multivariate analysis identified tumor number < 5 nodules [odds ratio 10.651, 95% confidence interval (CI) 2.168-52.317; P = 0.004] as an independent predictor of response and des-gamma-carboxyprothrombin level < 100 mAU/mL [hazard ratio (HR), 0.268, 95% CI 0.091-0.786, P = 0.017] and therapeutic effect CR or PR (HR 0.255, 95% CI 0.099-0.659; P = 0.005) as independent predictors of survival.
Transcatheter arterial infusion chemotherapy using lipiodol and DSMs might be considered as a potential intervention in HCC patients, especially those with tumors of < 5 nodules.

DOI： 10.1007/s00535-012-0537-8

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Therapeutic Potential of Canine Bone Marrow Stromal Cells (BMSCs) in the Carbon Tetrachloride (CCl4) Induced Chronic Liver Dysfunction Mouse Model 査読

Tomoya Haraguchi, Kenji Tani, Ryo Takagishi, Yasutaka Oda, Kazuhito Itamoto, Naoki Yamamoto, Shuji Terai, Isao Sakaida, Hiroshi Nakazawa, Yasuho Taura

JOURNAL OF VETERINARY MEDICAL SCIENCE 74 ( 5 ) 607 - 611 2012年5月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：JAPAN SOC VET SCI

Regenerative medicine using bone marrow cells is an attractive therapy for the cure of patients with severe liver disease. Here, we show the therapeutic potential of canine bone marrow stromal cells (BMSCs) in mouse models of CCl4-induced chronic liver dysfunction. We used two different models for xenotransplantation, nude mice and cyclosporine A (CSA) immunosuppressed mice. Serum parameters from a standard liver panel were not improved following transplantation. However, fibrotic liver lesions with severe inflammation were decreased in CCl4-treated CSA mice following BMSC transplantation. Effective migration of transplanted canine BMSCs was limited to persistently injured liver in CCl4-treated CSA mice, where they may be effective in resolving inflammatory fibrotic lesions. These results suggest that canine BMSCs are an effective cell source for liver regeneration.

DOI： 10.1292/jvms.11-0505

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Stem cell therapy in chronic liver disease 査読

Taro Takami, Shuji Terai, Isao Sakaida

CURRENT OPINION IN GASTROENTEROLOGY 28 ( 3 ) 203 - 208 2012年5月

記述言語：英語出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS

Purpose of review
To provide an overview of the current status of liver regeneration therapies for liver cirrhosis and future prospects.
Recent findings
Various clinical studies for liver disease have been reported, including hepatic administration of autologous CD34-positive cells induced by granulocyte colony-stimulating factor, portal vein administration of CD133-positive mononuclear cells, and administration of autologous bone marrow-derived mesenchymal stem cells. Effectiveness of these approaches has been shown in some patients. We have also reported improved liver fibrosis and function with infusion of autologous bone marrow cells in a basic study with mice, and on the basis of those results started autologous bone marrow cell infusion (ABMi) therapy for liver cirrhosis. The efficacy and safety of ABMi therapy has also been reported by other institutions.
Summary
Results of recent clinical studies strongly suggest that liver function-improving effects can be achieved using infusion of bone marrow (stem) cells for cirrhosis. New treatment methods using less-invasive bone marrow-derived cultured cells need to be developed.

DOI： 10.1097/MOG.0b013e3283521d6a

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Timeline for development of autologous bone marrow infusion (ABMi) therapy and perspective for future stem cell therapy 査読

Shuji Terai, Haruko Tanimoto, Masaki Maeda, Junichi Zaitsu, Takuro Hisanaga, Takuya Iwamoto, Koichi Fujisawa, Yuko Mizunaga, Toshihiko Matsumoto, Yohei Urata, Yoshio Marumoto, Isao Hidaka, Tsuyoshi Ishikawa, Yuichiro Yokoyama, Koji Aoyama, Masako Tsuchiya, Taro Takami, Kaoru Omori, Naoki Yamamoto, Makoto Segawa, Koichi Uchida, Takahiro Yamasaki, Kiwamu Okita, Isao Sakaida

JOURNAL OF GASTROENTEROLOGY 47 ( 5 ) 491 - 497 2012年5月

記述言語：英語出版者・発行元：SPRINGER TOKYO

Liver cirrhosis patients generally progress to liver failure. To cure this progressive disease, we developed a novel cell therapy using bone marrow cells; autologous bone marrow cell infusion (ABMi) therapy. We previously described the possible action mechanism of ABMi therapy in the cirrhotic liver, and showed the timeline and results of clinical studies of ABMi therapy. We have also carried out other clinical studies using bone marrow cells and granulocyte colony-stimulating factor. Here, we report a new randomized clinical trial to evaluate the effects of ABMi therapy. However, ABMi therapy may not be possible in patients who are unable to undergo general anesthesia; therefore, we have started to develop a next-generation stem cell therapy using cultured mesenchymal stem cells.

DOI： 10.1007/s00535-012-0580-5

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Ezetimibe reduces fatty acid quantity in liver and decreased inflammatory cell infiltration and improved NASH in medaka model 査読

Toshiyuki Oishi, Shuji Terai, Shinya Kuwashiro, Koichi Fujisawa, Toshihiko Matsumoto, Hiroshi Nishina, Isao Sakaida

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 422 ( 1 ) 22 - 27 2012年5月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：ACADEMIC PRESS INC ELSEVIER SCIENCE

Purpose: We previously developed medaka non-alcoholic steatohepatitis (NASH) model. The model showed similar histology with human NASH so we analyzed the effect of drug using medaka NASH activity score (MNAS). In this study we analyzed the effect of ezetimibe, a small intestine cholesterol transporter inhibitor, on NASH.
Methods: Medaka NASH model showed steatohepatits with infiltration of D-PAS positive inflammatory cell. In this study we induced medaka NASH and compared the effect of ezetimibe on medaka NASH by HFD.
Results: As compared with the HFD group, ezetimibe reduced total cholesterol and triacyglycerol in the blood. But concerning with liver quantity of fatty acids in the liver were significantly decreased by ezetimibe. Genes related with fatty acid metabolism in liver was also decreased by ezetimibe administration. On histological observations of the liver, increases in the number of inflammatory cells and MNAS were inhibited. With this decrease of fatty acid in liver, medaka NASH was improved by ezetimibe.
Conclusion: Ezetimibe was clarified as a useful drug to improve NASH. (C) 2012 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.bbrc.2012.04.087

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Matrix Metalloproteinases (MMPs) Activity in Cultured Canine Bone Marrow Stromal Cells (BMSCs) 査読

Tomoya Haraguchi, Kenji Tani, Masato Koga, Yasutaka Oda, Kazuhito Itamoto, Naoki Yamamoto, Shuji Terai, Isao Sakaida, Hiroshi Nakazawa, Yasuho Taura

JOURNAL OF VETERINARY MEDICAL SCIENCE 74 ( 5 ) 633 - 636 2012年5月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：JAPAN SOC VET SCI

Autologous bone marrow stromal cells (BMSCs) infusion therapy improves the hepatic fibrosis. To investigate the mechanism of remission, we evaluated the matrix metalloproteinase (MMP)-2 and -9 activity in canine BMSCs and the effect of pro-inflammatory cytokines on their expression. The activity and the gene expression of MMPs were analyzed by gelatin zymography and quantitative RT-PCR, respectively. The specific gelatinase bands were indicative effect of MMP-2 and -9 in canine BMSCs. MMP-2 expression seemed to be increased by TNF-alpha and IL-1 beta while MMP-9 was enhanced by TNF-alpha and IL-6. These results suggested that remissive effect on liver fibrosis might be partly attributable to the MMP-2 and -9 activity in BMSCs under the inflammatory condition.

DOI： 10.1292/jvms.11-0395

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Clear cell typeの肝細胞癌の一例

土屋昌子, 石川剛, 高見太郎, 寺井崇二, 山崎隆弘, 坂井田功

超音波医学 39 ( Suppl. ) S408 - S408 2012年4月

Splenectomy enhances the anti-fibrotic effect of bone marrow cell infusion and improves liver function in cirrhotic mice and patients 査読

Takuya Iwamoto, Shuji Terai, Yuko Mizunaga, Naoki Yamamoto, Kaoru Omori, Koichi Uchida, Takahiro Yamasaki, Yasuhiko Fujii, Hiroshi Nishina, Isao Sakaida

JOURNAL OF GASTROENTEROLOGY 47 ( 3 ) 300 - 312 2012年3月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：SPRINGER TOKYO

Background In 2003, we initiated a clinical trial to examine autologous bone marrow cell infusion (ABMi) therapy for cirrhotic patients and reported the clinical effect of the therapy. To analyze how splenectomy may potentiate the effects of bone marrow cell infusion on cirrhosis, we performed a mouse study and a clinical trial on patients with cirrhosis.
Methods In mice, we analyzed the effect of splenectomy on bone marrow cell infusion in four experimental groups (group A, splenectomy + bone marrow cell infusion + CCl4; group B, sham operation + bone marrow cell infusion + CCl4; group C, splenectomy + CCl4; group D, sham operation + CCl4). In clinical, we compared the effect of splenectomy on ABMi therapy.
Results We observed significantly increased average serum albumin levels and higher expression of green fluorescent protein (GFP), matrix metalloproteinase 9 (MMP9), and proliferating cell nuclear antigen in the livers of group A. We observed MMP9/GFP double-positive cells in the cirrhotic livers. A significant decrease in the liver fibrosis areas was observed in group A. Splenectomy enhanced the repopulation of bone marrow cells into the cirrhotic liver and improved the liver microenvironment via expression of MMP9 secreted from repopulating GFP-positive cells. Next, we performed a clinical trial to compare the effect of splenectomy on the efficacy of ABMi therapy. Cirrhotic patients who underwent splenectomy before ABMi therapy tended to have a greater improvement in liver function.
Conclusion ABMi therapy with splenectomy may be an effective therapeutic modality for cirrhosis.

DOI： 10.1007/s00535-011-0486-7

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Autologous bone marrow cell infusions suppress tumor initiation in hepatocarcinogenic mice with liver cirrhosis 査読

Masaki Maeda, Taro Takami, Shuji Terai, Isao Sakaida

JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY 27 104 - 111 2012年3月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：WILEY-BLACKWELL

We have previously reported the efficacy and safety of autologous bone marrow cell infusion (ABMi) therapy for liver cirrhosis patients without hepatocellular carcinoma in a multicenter clinical trial. However, since liver cirrhosis is highly oncogenic, evaluation of the effects of ABMi on the mechanisms of hepatocarcinogenesis is of great importance. Therefore, frequent ABMi was performed in hepatocarcinogenic mice, and its effects on hepatocarcinogenesis were analyzed. The N-nitrosodiethylamine (DEN)/green fluorescent protein (GFP)-carbon tetrachloride (CCl4) model was developed by administering DEN once, followed by repeated administration of CCl4 intraperitoneally as for the control group. In the administration (ABMi) group, GFP-positive bone marrow cells were infused through a tail vein. The kinetics of hepatocarcinogenesis were evaluated histologically 4.5 months after DEN treatment. At 4.5 months, there was significantly lower incidence of foci and tumors in the ABMi group, and they were smaller in number, while their size was almost equal. No GFP-positive tumors were found in ABMi livers. Moreover, ABMi livers showed significantly reduced liver fibrosis, consistent with significantly lower 8-hydroxy-2'-deoxyguanosine levels, higher superoxide dismutase activity, and increased nuclear translocation of nuclear factor-erythroid 2 p45-related factor 2. These results demonstrate that frequent ABMi might contribute to suppressed tumor initiation during stages of hepatocarcinogenesis, consistent with improvements in liver fibrosis and stabilization of redox homeostasis.

DOI： 10.1111/j.1440-1746.2011.07016.x

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Hepatic arterial infusion chemotherapy in combination with pegylated interferon-α-2b for advanced hepatocellular carcinoma. 査読

Okita K, Yamasaki T, Hamabe S, Saeki I, Harima Y, Terai S, Sakaida I

Hepato-gastroenterology 59 ( 114 ) 533 - 537 2012年3月

当科における肝細胞癌に対するsorafenibの治療成績

浦田洋平, 山崎隆弘, 在津潤一, 日高勲, 石川剛, 土屋昌子, 内田耕一, 寺井崇二, 坂井田功

日本消化器病学会雑誌 109 ( 臨増総会 ) A281 - A281 2012年3月

肝臓肝臓の再生治療

高見太郎, 寺井崇二, 坂井田功

Annual Review消化器 2012 192 - 197 2012年1月

記述言語：日本語出版者・発行元：(株)中外医学社

非代償性肝硬変症に対する現時点での根治療法は肝移植であるが,慢性的ドナー不足,手術侵襲や免疫拒絶などの諸問題は依然として解決されていない.一方,臨床研究としての肝臓再生療法はこれまでに,G-CSFで誘導した自己末梢血CD34陽性細胞の経肝動脈投与,CD133陽性単核球細胞の経門脈投与や,自己骨髄間葉系幹細胞投与による細胞療法などが報告され,一部の症例での改善が報告されている.また我々も,マウス基礎研究により自己骨髄細胞投与が肝線維化および肝機能を改善させることを報告し,その成果を基盤にした臨床研究「肝硬変症に対する自己骨髄細胞投与療法autologous bone marrow cell infusion therapy(ABMi療法)」でも肝機能改善・修復効果を確認した.さらに国内外からABMi療法の安全性・有効性が追試報告されるなど,自己骨髄由来細胞を用いた肝硬変症に対する再生治療の有効性が強く示唆されている.(著者抄録)

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