2019 Fiscal Year Annual Research Report
Analysis of liver repairing and regenerative capability of adipose tissue-derived stem cells obtained from the host with chronic liver disease
| Project/Area Number |
17K09413
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| Research Institution | Kanazawa University |
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Principal Investigator |
酒井 佳夫 金沢大学, 医学系, 准教授 (80401925)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Keywords | 間葉系幹細胞 / 脂肪組織 / 慢性肝疾患 |
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| Outline of Annual Research Achievements |
慢性肝疾患には、B型・C型ウイルス性肝炎による慢性肝炎、原発性胆汁性胆管炎、自己免疫性肝炎、アルコール性肝炎、非アルコール施肥脂肪性肝炎(NASH)がある。これら慢性肝疾患は、その原因が除去あるいはコントロールされないと、重篤な合併症を伴う肝硬変状態に至る。特に、NASH・肝硬変は、近年増加し続けて重要な課題となってきている。これまでに我々は、多分化能および免疫修飾機能を有する間葉系幹細胞について、その投与による肝炎、肝硬変に対する治療の可能性を示してきた。また、医師主導治験として、「肝硬変に対する自己皮下脂肪組織由来再生（幹）細胞の経肝動脈投与による肝再生療法の有効性おより安全性を検討する多施設共同非盲検非対照試験」を実施した。治験は自己由来の細胞を投与することから、本研究では、肝疾患状態にある成体の脂肪組織由来間葉系幹細胞、間質細胞の特性を解析することを目的に、動脈硬化高脂肪食（AT-HF)給餌によるNASH・肝硬変マウスモデル、および単純性脂肪肝(SS)マウスモデル（給餌後4週、12週後）より脂肪組織由来間質細胞群を経時的に採取し、非培養の細胞の幹細胞関連の抗原等をFlow cytometryにて解析した。Flow cytometryでは、FSC/SSC small(Fraction 1)、FSC/SSC middle (Fraction 2)、FSC/SSC large(Fraction 3)の、３つの亜分画について解析した。Fraction 1とFraction 3では、CD29抗原陽性細胞を各マウス間に差がなく高く発現していた。CD44の発現はFraction 2においてCD45およびCD44抗原に、NASHおよびSSマウスで経時的変化を認めた。また、NASH進展および非進展状態マウスの非培養脂肪組織間質細胞の遺伝子発現プロファイルに差があることが示唆された。
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Research Products
(23 results)
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[Journal Article] Regenerative Therapy for Liver Cirrhosis Based on Intrahepatic Arterial Infusion of Autologous Subcutaneous Adipose Tissue-Derived Regenerative (Stem) Cells: Protocol for a Confirmatory Multicenter Uncontrolled Clinical Trial.2020
Author(s)
Y Sakai, S Fukunishi, M Takamura, O Inoue, S Takashima, S Usui, A Seki, A Nasti, T Ho, K Kawaguchi, A Asai, Y Tsuchiimura, T Muraymoto, T Yamashita, T Yamashita, E Mizukoshi, M Honda, Y Imai, K Yoshama, T Wada, K Harada, K Higuchi, S Kaneko
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Journal Title
JMIR Res Protoc
Volume: 9
Pages: e17904
DOI
Peer Reviewed / Open Access
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[Journal Article] Surrogacy of Time to Progression for Overall Survival in Advanced Hepatocellular Carcinoma Treated with Systemic Therapy: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.2019
Author(s)
Terashima T, Yamashita T, Toyama T, Arai K, Kawaguchi K, Kitamura K, Yamashita T, Sakai Y, Mizukoshi E, Honda M, Kaneko S.
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Journal Title
Liver Cancer.
Volume: 8
Pages: 130-139
DOI
Peer Reviewed / Open Access
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[Journal Article] Induction of Selenoprotein P mRNA during Hepatitis C Virus Infection Inhibits RIG-I-Mediated Antiviral Immunity2019
Author(s)
Murai K, Honda M, Shirasaki T, Shimakami T, Omura H, Misu H, Kita Y, Takeshita Y, Ishii KA, Takamura T, Urabe T, Shimizu R, Okada H, Yamashita T, Sakai Y, Kaneko S.
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Journal Title
Cell Host Microbe.
Volume: 25
Pages: 588-601
DOI
Peer Reviewed
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[Journal Article] Characteristics of impaired dendritic cell function in patients with hepatitis B virus infection.2019
Author(s)
Yonejima A, Mizukoshi E, Tamai T, Nakagawa H, Kitahara M, Yamashita T, Arai K, Terashima T, Iida N, Fushimi K, Okada H, Yamashita T, Sakai Y, Honda M, Kaneko S.
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Journal Title
Hepatology.
Volume: 70
Pages: 25-39
DOI
Peer Reviewed
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[Journal Article] Adipose tissue-derived stem cells prevent fibrosis in murine steatohepatitis by suppressing IL-17-mediated inflammation.2019
Author(s)
Yamato M, Sakai Y, Mochida H, Kawaguchi K, Takamura M, Usui S, Seki A, Mizukoshi E, Yamashita T, Yamashita T, Ishida K, Nasti A, Tuyen HTB, Komura T, Yoshida K, Wada T, Honda M, Kaneko S.
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Journal Title
J Gastroenterol Hepatol
Volume: 34
Pages: 1432-1440
DOI
Peer Reviewed
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[Journal Article] Biological characteristics of gene expression features in pancreatic cancer cells induced by proton and X-ray irradiation.2019
Author(s)
Haruo Fujinaga, Yoshio Sakai, Tatsuya Yamashita, Kuniaki Arai, Takeshi Terashima, Takuya Komura, Akihiro Seki, Kazunori Kawaguchi, Alessandro Nasti, Keiko Yoshida, Takashi Wada, Kazutaka Yamamoto, Kyo Kume, Takashi Hasegawa, Takushi Takatae, Masao Honda, and Shuichi Kaneko.
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Journal Title
Int J Radiat Biol.
Volume: 95
Pages: 571-579
DOI
Peer Reviewed
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[Journal Article] Development of novel diagnostic system for pancreas cancer including early stages measuring mRNA of whole blood cells.2019
Author(s)
Sakai Y, Honda M, Matsui S, Komori O, Murayama T, Fujiwara T, Mizuno M, Imai Y, Yoshimura K, Nasti A, Wada T, Iida N, Kitahara M, Horii R, Tamai T, Nishikawa M, Okafuji H, Mizukoshi E, Yamashita T, Yamashita T, Arai K, Kitamura K, Kawaguchi K, Takatori H, Shimakami T, Terashima T, Hayashi T, Nio K, Kaneko S, et al
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Journal Title
Cancer Sci.
Volume: 110
Pages: 1364-1388
DOI
Peer Reviewed
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[Journal Article] Distinct chemotherapy-associated anti-cancer immunity by myeloid cells inhibition in murine pancreatic cancer models.2019
Author(s)
Sakai Y, Miyazawa M, Komura T, Yamada T, Nasti A, Yoshida K, Takabatake H, Yamato M, Yamashita T, Yamashita T, Mizukoshi E, Okuzono M, Ho TTB, Kawaguchi K, Wada T, Honda M, Kaneko S.
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Journal Title
Cancer Sci.
Volume: 110
Pages: 903-912
DOI
Peer Reviewed
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[Journal Article] Three renal failure cases successfully treated with ombitasvir/paritaprevir/ritonavir for genotype 1b hepatitis C virus reinfection after liver transplantation.2019
Author(s)
Orita N, Shimakami T, Sunagozaka H, Horii R, Nio K, Terashima T, Iida N, Kitahara M, Takatori H, Kawaguchi K, Kitamura K, Arai K, Yamashita T, Sakai Y, Yamashita T, Mizukoshi E, Honda M, Kaneko S.
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Journal Title
Clin J Gastroenterol.
Volume: 12
Pages: 63-70
DOI
Peer Reviewed
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[Journal Article] Notch signaling facilitates hepatitis B virus covalently closed circular DNA transcription via cAMP response element-binding protein with E3 ubiquitin ligase-modulation.2019
Author(s)
Wang Z, Kawaguchi K, Honda M, Hashimoto S, Shirasaki T, Okada H, Orita N, Shimakami T, Yamashita T, Sakai Y, Mizukoshi E, Murakami S, Kaneko S.
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Journal Title
Sci Rep
Volume: 9
Pages: 1621
DOI
Peer Reviewed / Open Access
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[Journal Article] Serum aldo-keto reductase family 1 member B10 predicts advanced liver fibrosis and fatal complications of nonalcoholic steatohepatitis.2019
Author(s)
Kanno M, Kawaguchi K, Honda M, Horii R, Takatori H, Shimakami T, Kitamura K, Arai K, Yamashita T, Sakai Y, Yamashita T, Mizukoshi E, Kaneko S.
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Journal Title
J Gastroenterol.
Volume: 54
Pages: 549-557
DOI
Peer Reviewed
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