研究者詳細 - 寺井　崇二

Current State and Future Prospects for Our Liver Regeneration Therapy Using Autologous Bone Marrow Cells for Decompensated Liver Cirrhosis Patients 査読

Taro Takami, Shuji Terai, Isao Sakaida

JOURNAL OF PHARMACOLOGICAL SCIENCES 115 ( 3 ) 274 - 278 2011年3月

記述言語：英語出版者・発行元：JAPANESE PHARMACOLOGICAL SOC

We have developed an in vivo mouse model [the green fluorescent protein (GFP) /carbon tetrachloride (CCl4) model] and reported that infused G FP-positive bone marrow cells administered via a tail vein efficiently repopulated cirrhotic liver tissue under conditions of persistent liver damage induced by CCl4. Moreover, bone marrow cells infused into the liver improved liver function and ameliorated liver fibrosis with higher expression of matrix metalloproteinase 9 (MMP-9), consistent with improved survival rate. Based on these findings, we started a multicenter clinical trial of autologous bone marrow cell infusion (ABMi) therapy for decompensated liver cirrhosis patients and demonstrated the efficacy of this approach without unexpected complications. However, this therapy involves bone marrow aspiration under general anesthesia and is not indicated for patients for whom general anesthesia is difficult. We therefore aimed to develop a new liver regeneration therapy in which cells having a curative effect on liver cirrhosis are isolated and cultured from a small amount of autologous bone marrow aspirated under local anesthesia and infused back into the same subject. Herein, we present results for the GFP/CCl4 model and ABMi therapy and future prospects for a new liver regeneration therapy.

DOI： 10.1254/jphs.10R13FM

非代償性肝硬変の合併症とその対策肝硬変症に対する次世代型骨髄由来培養細胞を用いた修復再生療法の開発

寺井崇二, 高見太郎, 坂井田功

日本消化器病学会雑誌 108 ( 臨増総会 ) A147 - A147 2011年3月

当科で経験したHBVキャリア急性増悪を来たした二例

内田耕一, 瀬川誠, 柴田大明, 植木谷俊之, 播磨陽平, 土屋昌子, 石川剛, 寺井崇二, 山崎隆弘, 坂井田功, 加藤彰, 木村輝明, 山下智省, 沖田極

肝臓 52 ( 3 ) 222 - 222 2011年3月

Autologous bone marrow cell infusion therapy for liver cirrhosis patients 査読

Shuji Terai, Isao Sakaida

JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 18 ( 1 ) 23 - 25 2011年1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

We developed a novel cell therapy, autologous bone marrow cell infusion (ABMi) therapy, using autologous bone marrow, for liver cirrhosis patients. Our study depends on the findings from basic studies that bone marrow cell infusion repairs liver fibrosis in the cirrhotic liver, and improves liver function and the survival rate. Beginning in November 2003, we started a clinical study and found that ABMi therapy was safe and effective for liver cirrhosis patients. Multicenter trials in Japan and Korea have also shown the effectiveness of ABMi therapy. In this review, we report the current status of ABMi therapy for liver cirrhosis patients.

DOI： 10.1007/s00534-010-0305-1

Efficient detection of hepatocellular carcinoma by a hybrid blood test of epigenetic and classical protein markers 査読

Norio Iizuka, Masaaki Oka, Isao Sakaida, Toyoki Moribe, Toshiaki Miura, Naoki Kimura, Shigeru Tamatsukuri, Hideo Ishitsuka, Koichi Uchida, Shuji Terai, Satoyoshi Yamashita, Kiwamu Okita, Koichiro Sakata, Yoshiyasu Karino, Joji Toyota, Eiji Ando, Tatsuya Ide, Michio Sata, Ryoichi Tsunedomi, Masahito Tsutsui, Michihisa Iida, Yoshihiro Tokuhisa, Kazuhiko Sakamoto, Takao Tamesa, Yusuke Fujita, Yoshihiko Hamamoto

CLINICA CHIMICA ACTA 412 ( 1-2 ) 152 - 158 2011年1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：ELSEVIER SCIENCE BV

Background: There are few blood tests for an efficient detection of hepatocellular carcinoma (HCC) associated with hepatitis C virus (HCV) infection.
Methods: The abilities of quantitative analyses of 7 genes hypermethylation in serum DNA, a-fetoprotein (AFP) and prothrombin-induced vitamin K absence II (PIVKA-II), and various combinations to detect HCC were evaluated in a training cohort of 164 HCV-infected patients (108 HCCs; 56 non-HCCs). An optimal hybrid detector, built using data for 2 methylated genes (SPINT2 and SRD5A2), AFP, and PIVKA-II. achieved the most satisfactory ability to detect HCC in the training cohort. We evaluated the ability of the optimal hybrid detector to detect HCC in an independent validation cohort of 258 consecutive HCV-infected patients (112 HCCs; 146 non-HCCs) who were newly enrolled in 4 distinct institutes.
Results: In the validation cohort of 258 patients, accuracy, sensitivity, and specificity of the hybrid detector for detection of HCC were 81.4%, 73.2%, and 87.7%, respectively. Notably, even when detecting HCC <= 2 cm in diameter, the hybrid detector maintained markedly high abilities (84.6% accuracy, 72.2% sensitivity, 87.7% specificity). Youden's index (sensitivity + specificity - 1) for HCC <= 2 cm was 0.60, vastly much superior to the 0.39 for AFP at a cut-off value of 20 ng/ml and the 0.28 for PIVKA-II at a cut-off value of 40 mAU/ml.
Conclusions: These results show that the optimal hybrid blood detector can detect HCV-related HCC more accurately. (C) 2010 Elsevier B.V. All rights reserved.

DOI： 10.1016/j.cca.2010.09.028

肝臓肝疾患の再生治療

高見太郎, 寺井崇二, 坂井田功

Annual Review消化器 2011 223 - 228 2011年1月

記述言語：日本語出版者・発行元：(株)中外医学社

非代償性肝硬変症の根治療法は肝移植である.2010年7月,家族の承諾による脳死臓器提供を認めた改正臓器移植法が全面施行されたが,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,これまでに肝臓再生修復療法の細胞源として骨髄由来(幹)細胞が注目され,G-CSFにより誘導された自己CD34陽性細胞を用いた細胞療法,CD133陽性単核球細胞の門脈内投与療法や,自己間葉系幹細胞投与による細胞療法などの報告がある.我々は,骨髄細胞から肝細胞への分化・増殖評価マウスモデル(GFP/CCl4モデル)により自己骨髄細胞投与が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.さらに海外で共同実施したABMi療法の臨床研究の結果,自己骨髄由来細胞を用いた肝硬変症に対する再生治療・細胞療法の有効性が明らかになった.(著者抄録)

C型慢性肝炎におけるエラストグラフィの有用性

江角智子, 高見太郎, 岸田由香里, 堤寛子, 松尾亜矢, 石川剛, 瀬川誠, 寺井崇二, 山崎隆弘, 坂井田功

超音波医学 37 ( 6 ) 679 - 679 2010年11月

Sonazoid造影エコー検査では肝細胞癌との鑑別が困難であった脈絡膜悪性黒色腫肝転移の一例

大石俊之, 石川剛, 土屋昌子, 高見太郎, 内田耕一, 寺井崇二, 山崎隆弘, 坂井田功

超音波医学 37 ( 6 ) 676 - 677 2010年11月

門脈圧亢進症における病態進行度の指標としての肝弾性値の有用性

瀬川誠, 浜辺功一, 石川剛, 寺井崇二, 山崎隆弘, 坂井田功

超音波医学 37 ( 6 ) 679 - 679 2010年11月

Helicobacter pylori CagA inhibits endocytosis of cytotoxin VacA in host cells 査読

Junko K. Akada, Hiroki Aoki, Yuji Torigoe, Takao Kitagawa, Hisao Kurazono, Hisashi Hoshida, Jun Nishikawa, Shuji Terai, Masunori Matsuzaki, Toshiya Hirayama, Teruko Nakazawa, Rinji Akada, Kazuyuki Nakamura

DISEASE MODELS & MECHANISMS 3 ( 9-10 ) 605 - 617 2010年9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：COMPANY OF BIOLOGISTS LTD

Helicobacter pylori, a common pathogen that causes chronic gastritis and cancer, has evolved to establish persistent infections in the human stomach. Epidemiological evidence suggests that H. pylori with both highly active vacuolating cytotoxin A (VacA) and cytotoxin-associated gene A (CagA), the major virulence factors, has an advantage in adapting to the host environment. However, the mechanistic relationship between VacA and CagA remains obscure. Here, we report that CagA interferes with eukaryotic endocytosis, as revealed by genome-wide screening in yeast. Moreover, CagA suppresses pinocytic endocytosis and the cytotoxicity of VacA in gastric epithelial cells without affecting clathrin-dependent endocytosis. Our data suggest that H. pylori secretes VacA to attack distant host cells while injecting CagA into the gastric epithelial cells to which the bacteria are directly attached, thereby protecting these attached host cells from the cytotoxicity of VacA and creating a local ecological niche. This mechanism might allow H. pylori to balance damage to one population of host cells with the preservation of another, allowing for persistent infection.

DOI： 10.1242/dmm.004879