Gene transfer programming of mesenchymal stem cells for repairing and regeneration of the liver, and its application for liver regeneration therapy

• Project/Area Number: 23590968
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Kanazawa University
• Principal Investigator: SAKAI Yoshio 金沢大学, 医学系, 准教授 (80401925)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2011: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 肝臓学 / 肝再生 / 間葉系幹細胞 / 遺伝子導入 / エレクトロポレーション

Research Abstract

The experimental trial of differentiation of adipose-tissue derived stromal cells to hepatocyte by means of gene transduction was conducted. The pCMV6-HNF4a-GFP expressing GFP-tagged HNF4a and the pCMV6-HNF1b-GFP expressing GFP-tagged HNF1b was transduced to adipose tissue-derived stromal cells by electroporation method. Cells at day 15 after transduction was assessed for gene expression by real-time detective PCR. Cells transduced with pCMV6-HNF4a-GFP expressed HNF4a, however, did not express albumin. Cells transduced with pCMV6-HNF1b-GFP neither expressed HNF1b nor albumin. Improvement is required for differentiation of adipose tissue derived stromal cells by electroporation method.

Research Products

• [Journal Article] Adipose tissue derived stromal stem cell therapy in murine ConA-derived hepatitis is dependent on myeloid-lineage and CD4+ T-cell suppression (2013)
  • Author(s): Higashimoto M, Sakai Y, Takamura M, Usui S, Nasti A, Yoshida K, Seki A, Komura T, Honda M, Wada T, Furuichi K, Ochiya T, Kaneko S
  • Journal Title: Eur J Immunol Volume: vol.43 Pages: 2956-2968
  • Peer Reviewed
• [Journal Article] Adipose tissue-derived stem cells as a regenerative therapy for a mouse steatohepatitis-induced cirrhosis model (2013)
  • Author(s): Seki A, Sakai Y, Komura T, Nasti A, Yoshida K, Higashimoto M, Honda M, Usui S, Takamura M, Takamura T, Ochiya T, Furuichi K, Wada T, Kaneko S
  • Journal Title: Hepatology Volume: vol. 58 Pages: 1133-1142
• [Journal Article] Nodular lesions and mesangiolysis in diabetic nephropathy (2013)
  • Author(s): Wada T, Shimizu M, Yokoyama H, Iwata Y, Sakai Y, Kaneko S, Furuichi K
  • Journal Title: Clin Exp Nephrol Volume: vol.17 Pages: 3-9
  • NAID: 10031169438
  • Peer Reviewed
• [Journal Article] Adipose tissue derived stromal stem cell therapy in murine ConA-derived hepatitis is dependent on myeloid-lineage and CD4+ T-cell suppression. (2013)
  • Author(s): Higashimoto M, Sakai Y, Takamura M, Usui S, Nasti A, Yoshida K, Seki A, Komura T, Honda M, Wada T, Furuichi K, Ochiya T, Kaneko S.
  • Journal Title: Eur J Immunol Volume: 43 Issue: 11 Pages: 2956-68
  • DOI: 10.1002/eji.201343531
  • Peer Reviewed
• [Journal Article] Adipose tissue-derived stem cells as a regenerative therapy for a mouse steatohepatitis-induced cirrhosis model (2013)
  • Author(s): A Seki, S Y akai, T Komura, A Nasti, K Yoshida, M Higashimoto, M Honda, S Usui, M Takamura, T Takamura, T Ochiya, K Furuichi, T Wada, S Kaneko
  • Journal Title: Hepatology Volume: 58(3) Issue: 3 Pages: 1133-42
  • DOI: 10.1002/hep.26470
  • Peer Reviewed
• [Journal Article] Nodular lesions and mesangiolysis in diabetic nephropathy. (2013)
  • Author(s): Wada T, Shimizu M, Yokoyama H, Iwata Y, Sakai Y, Kaneko S, Furuichi K.
  • Journal Title: Clin Exp Nephrol. Volume: 17 Issue: 1 Pages: 3-9
  • DOI: 10.1007/s10157-012-0711-6
  • NAID: 10031169438
  • Peer Reviewed
• [Journal Article] Prediction formula for interrupter respiratory resistance in healthy Japanese adults (2012)
  • Author(s): Nakade Y, Fujimura M, Ohkura N, Okuizumi Y, Nakatas M, Nanbu Y, Oe H, Horita H, Sakai Y, Wada T
  • Journal Title: Rinsho Byori Volume: vol.60 Pages: 725-733
  • NAID: 10031123882
  • Peer Reviewed
• [Journal Article] Association of changes in the gene expression profile of blood cells with the local tumor inflammatory response in a murine tumor model (2012)
  • Author(s): Sakai Y, Tatsumi I, Higashimoto M, Seki A, Nasti A, Yoshida K, Kawaguchi K, Wada T, Honda M, Komura T, Kaneko S
  • Journal Title: Biochem Biophys Res Commun Volume: vol.428 Pages: 36-43
  • Peer Reviewed
• [Journal Article] Acyclic retinoid targets platelet-derived growth factor signaling in the prevention of hepatic fibrosis and hepatocellular carcinoma development (2012)
  • Author(s): Okada H, Honda M, Campbell JS, Sakai Y, Yamashita T, Takebuchi Y, Hada K, Shirasaki T, Takabatake R, Nakamura M, Sunagozaka H, Tanaka T, Fausto N, Kaneko S
  • Journal Title: Cancer Res Volume: vol.72 Pages: 4459-4471
  • Peer Reviewed
• [Journal Article] Beneficial effect of branched-chain amino acid supplementation on glycemic control in chronic hepatitis C patients with insulin resistance : implications for type 2 diabetes (2012)
  • Author(s): Takeshita Y, Takamura T, Kita Y, Ando H, UedaT, Kato K, Misu H, Sunagozaka H, Sakai Y, Yamashita T, Mizukoshi E, Honda M, Kaneko S
  • Journal Title: Metabolism Volume: vol.61 Pages: 1388-1394
  • NAID: 120004997025
  • Peer Reviewed
• [Journal Article] Effects of adipose-derived mesenchymal cells on ischemia-reperfusion injury in kidney (2012)
  • Author(s): Furuichi K, Shintani H, Sakai Y, Ochiya T, Matsushima K, Kaneko S, Wada T
  • Journal Title: Clin Exp Nephrol Volume: vol.16 Pages: 670-680
  • NAID: 10031122254
  • Peer Reviewed
• [Journal Article] Membrane-bound form of monocyte chemoattractant protein-1 enhances antitumor effects of suicide gene therapy in a model of hepatocellular carcinoma (2012)
  • Author(s): Marukawa Y, Nakamoto Y, Kakinoki K, Tsuchiyama T, Iida N, Kagaya T, Sakai Y, Naito M, Mukaida N, Kaneko S
  • Journal Title: Cancer Gene Ther Volume: vol.10 Pages: 312-319
  • NAID: 120003989046
  • Peer Reviewed
• [Journal Article] Prediction formula for interrupter respiratory resistance in healthy Japanese adults. (2012)
  • Author(s): Nakade Y, Fujimura M, Ohkura N, Okuizumi Y, Nakatas M, Nanbu Y, Oe H, Horita H, Sakai Y, Wada T.
  • Journal Title: Rinsho Byori Volume: 60 Pages: 725-733
  • NAID: 10031123882
  • Peer Reviewed
• [Journal Article] Association of changes in the gene expression profile of blood cells with the local tumor inflammatory response in a murine tumor model. (2012)
  • Author(s): Sakai Y, Tatsumi I, Higashimoto M, Seki A, Nasti A, Yoshida K, Kawaguchi K, Wada T, Honda M, Komura T, Kaneko S.
  • Journal Title: Biochem Biophys Res Commun. Volume: 428 Issue: 1 Pages: 36-43
  • DOI: 10.1016/j.bbrc.2012.10.004
  • Peer Reviewed
• [Journal Article] Acyclic retinoid targets platelet-derived growth factor signaling in the prevention of hepatic fibrosis and hepatocellular carcinoma development. (2012)
  • Author(s): Okada H, Honda M, Campbell JS, Sakai Y, Yamashita T, Takebuchi Y, Hada K, Shirasaki T, Takabatake R, Nakamura M, Sunagozaka H, Tanaka T, Fausto N, Kaneko S.
  • Journal Title: Cancer Res. Volume: 72 Issue: 17 Pages: 4459-4471
  • DOI: 10.1158/0008-5472.can-12-0028
  • Peer Reviewed
• [Journal Article] Beneficial effect of branched-chain amino acid supplementation on glycemic control in chronic hepatitis C patients with insulin resistance : Implications for type 2 diabetes. Metabolism (2012)
  • Author(s): Honda M, (他12名, 12番目)
  • Journal Title: Epub ahead of print Volume: (Epub ahead of print) Issue: 10 Pages: 1388-94
  • DOI: 10.1016/j.metabol.2012.03.011
  • Peer Reviewed
• [Journal Article] Effects of adipose-derived mesenchymal cells on ischemia-reperfusion injury in kidney. (2012)
  • Author(s): Furuichi K, Shintani H, Sakai Y, Ochiya T, Matsushima K, Kaneko S, Wada T.
  • Journal Title: 10.1007/s10157-012-0614-6. Volume: 16 Pages: 670-689
  • NAID: 10031122254
  • Peer Reviewed
• [Journal Article] Membrane-bound form of monocyte chemoattractant protein-1 enhances antitumor effects of suicide gene therapy in a model of hepatocellular carcinoma. (2012)
  • Author(s): Marukawa Y, Nakamoto Y, Kakinoki K, Tsuchiyama T, Iida N, Kagaya T, Sakai Y, Naito M, Mukaida N, Kaneko S.
  • Journal Title: 10.1038/cgt.2012.3. Volume: 19 Pages: 312-319
  • NAID: 120003989046
  • Peer Reviewed
• [Journal Article] Frequency of CD45RO+ subset in CD4+CD25(high) regulatory T cells associated with progression ofhepatocellular carcinoma (2011)
  • Author(s): Takata Y, Nakamoto Y, Nakada A, Terashima T, Arihara F, Kitahara M, Kakinoki K, Arai K. Yamashita T, Sakai Y, Yamashita T, Mizukoshi E, Kaneko S
  • Journal Title: Cancer Lett Volume: vol.307 Pages: 165-173
  • Peer Reviewed
• [Journal Article] Comparative analysis of various tumor-associated antigen-specific t-cell responses in patients with hepatocellular carcinoma (2011)
  • Author(s): Mizukoshi E, Nakamoto Y, Arai K, Yamashita T, Sakai A, Sakai Y, Kagaya T, Yamashita T, Honda M, Kaneko S
  • Journal Title: Hepatology Volume: vol.53 Pages: 1206-1216
  • Peer Reviewed
• [Journal Article] Malnutrition impairs interferon signaling through mTOR and FoxO pathways in patients with chronic hepatitis C (2011)
  • Author(s): Honda M, Takehana K, Sakai A, Tagata Y, Shirasaki T, Nishitani S, Muramatsu T, Yamashita T, Nakamoto Y, Mizukoshi E, Sakai Y, Yamashita T, Nakamura M, Shimakami T, Yi M, Lemon SM, Suzuki T, Wakita T, Kaneko S; Hokuriku Liver Study Group
  • Journal Title: Gastroenterology Volume: vol.141 Pages: 128-140
  • Peer Reviewed
• [Journal Article] Frequency of CD45RO+ subset in CD4+CD25(high) regulatory T cells associated with progression of hepatocellular carcinoma. (2011)
  • Author(s): Takata Y, Nakamoto Y, Nakada A, Terashima T, Arihara F, Kitahara M, Kakinoki K, Arai K, Yamashita T, Sakai Y, Yamashita T, Mizukoshi E, Kaneko S.
  • Journal Title: Cancer Lett Volume: 307 Pages: 165-173
  • NAID: 120003141809
  • Peer Reviewed
• [Journal Article] Comparative analysis of various tumor-associated antigen-specific t-cell responses in patients with hepatocellular carcinoma. (2011)
  • Author(s): Mizukoshi E, Nakamoto Y, Arai K, Yamashita T, Sakai A, Sakai Y, Kagaya T, Yamashita T, Honda M, Kaneko S.
  • Journal Title: Hepatology Volume: 53 Pages: 1206-1216
  • Peer Reviewed
• [Journal Article] Malnutrition impairs interferon signaling through mTOR and FoxO pathways in patients with chronic hepatitis C. (2011)
  • Author(s): Honda M, Takehana K, Sakai A, Tagata Y, Shirasaki T, Nishitani S, Muramatsu T, Yamashita T, Nakamoto Y, Mizukoshi E, Sakai Y et al.
  • Journal Title: Gastroenterology Volume: 141 Pages: 128-140
  • Peer Reviewed
• [Presentation] 肝硬変マウスモデルにおける脂肪組織由来間質細胞投与による肝修復再生効果の検討 (2013)
  • Author(s): 酒井佳夫、関晃裕、金子周一
  • Organizer: 第40回日本肝臓学会西部会
  • Place of Presentation: 岐阜都ホテル、岐阜
  • Year and Date: 2013-12-06
• [Presentation] Features of immunomodulatory and therapeutic effects of mesenchymal stromal/stem cells on non-alcoholic steatohepatitis murine model in early and cirrhotic phases (2013)
  • Author(s): Akihiro Seki, Yoshio Sakai, Mami Higashimoto, Takuya Komura, Alessandro Nasti, Keiko Yoshida, Takahiro Ochiya, Takashi Wada, Masao Honda, Shuichi Kaneko
  • Organizer: The 64th Annual Meeting of the American Association for the Study of Liver Diseases
  • Place of Presentation: Washington D.C., U.S.A
  • Year and Date: 2013-11-04
• [Presentation] 脂肪組織由来間質細胞を用いた肝硬変に対する肝再生療法実用化への基礎的検討 (2013)
  • Author(s): 酒井佳夫、関晃裕、金子周一
  • Organizer: 第55回日本消化器病学会大会
  • Place of Presentation: グランドプリンスホテル新高輪、東京
  • Year and Date: 2013-10-10
• [Presentation] 肝硬変マウスモデルにおける脂肪組織由来幹細胞による肝修復再生療法の検討 (2013)
  • Author(s): 関晃裕、酒井佳夫、Alessandro Nasti、吉田佳子、東元真実、小村卓也、本多政夫、金子周一
  • Organizer: 第49回日本肝臓学会総会
  • Place of Presentation: 京王プラザホテル、東京
  • Year and Date: 2013-06-06
• [Presentation] 血液細胞の遺伝子発現解析による生体のがん反応解明と消化器癌診断法開発の可能性 (2013)
  • Author(s): 酒井佳夫、本多政夫、金子周一
  • Organizer: 第99回日本消化器病学会総会
  • Place of Presentation: 鹿児島
  • Year and Date: 2013-03-21
• [Presentation] マウス皮下肝癌モデルにおける末梢血液細胞の遺伝子発現プロファイルの変化 (2012)
  • Author(s): 酒井佳夫、金子周一、古市賢吾、和田隆志
  • Organizer: 第59回日本臨床検査医学会学術集会
  • Place of Presentation: 京都
  • Year and Date: 2012-11-30
• [Presentation] Therapeutic effect of adipose derived mesenchymal stem cell to murine NASH liver cirrhosis inactivating Kupffer/Macrophage and helper T cell (2012)
  • Author(s): Akihiro Seki, Yoshio Sakai, Takuya Komura, Mami Higashimoto, Haruo Fujinaga, Masao Honda,Takashi Wada, Toshinari Takamura, Takahiro Ochiya, Shuichi Kaneko
  • Organizer: The 63rd Annual Meeting of the American Association for the Study Liver Diseases
  • Place of Presentation: Boston
  • Year and Date: 2012-11-13
• [Presentation] 肝硬変に対する脂肪組織由来間質細胞による肝再生療法開発 (2012)
  • Author(s): 酒井佳夫、関晃裕、金子周一
  • Organizer: JDDW 2012シンポジウム11
  • Place of Presentation: 神戸ポートピアホテル
  • Year and Date: 2012-10-11
• [Presentation] 肪組織由来間質細胞を用いた肝硬変に対する肝再生療法実用化への基礎的検討
  • Author(s): 酒井佳夫、関晃裕、金子周一.
  • Organizer: 第55回日本消化器病学会大会
  • Place of Presentation: グランドプリンスホテル新高輪、東京
• [Presentation] 肝硬変マウスモデルにおける脂肪組織由来間質細胞投与による肝修復再生効果の検討
  • Author(s): 酒井佳夫、関晃裕、金子周一.
  • Organizer: 第40回日本肝臓学会西部会
  • Place of Presentation: 岐阜都ホテル、岐阜
• [Presentation] Features of immunomodulatory and therapeutic effects of mesenchymal stromal/stem cells on non-alcoholic steatohepatitis murine model in early and cirrhotic phases.
  • Author(s): Akihiro Seki, Yoshio Sakai, Mami Higashimoto, Takuya Komura, Alessandro Nasti, Keiko Yoshida, Takahiro Ochiya, Takashi Wada, Masao Honda, Shuichi Kaneko.
  • Organizer: The 64th Annual Meeting of the American Association for the Study of Liver Diseases
  • Place of Presentation: Washington D.C., U.S.A.
• [Presentation] 肝硬変マウスモデルにおける脂肪組織由来幹細胞による肝修復再生療法の検討
  • Author(s): 関晃裕、酒井佳夫 Alessandro Nasti, 吉田佳夫、東元真実、小村卓也、本多政夫、金子周一.
  • Organizer: 第49回日本肝臓学会総会
  • Place of Presentation: 京王プラザホテル、東京
• [Presentation] 肝硬変に対する脂肪組織由来間質細胞による肝再生療法開発
  • Author(s): 酒井佳夫、関晃裕、金子周一
  • Organizer: JDDW 2012 シンポジウム11
  • Place of Presentation: 神戸ポートピアホテル、兵庫県
• [Presentation] マウス皮下肝癌モデルにおける末梢血液細胞の遺伝子発現プロファイルの変化
  • Author(s): 酒井佳夫、金子周一、古市賢吾、和田隆志
  • Organizer: 第59回日本臨床検査医学会学術集会
  • Place of Presentation: 国立京都国際会館、京都府
• [Presentation] 血液細胞の遺伝子発現解析による生体のがん反応解明と消化器癌診断法開発の可能性
  • Author(s): 酒井佳夫、本多政夫、金子周一
  • Organizer: 第99回日本消化器病学会総会
  • Place of Presentation: 城山観光ホテル、鹿児島県
• [Presentation] Therapeutic effect of adipose derived mesenchymal stem cell to murine NASH liver cirrhosis inactivating Kupffer/Macrophage and helper T cell.
  • Author(s): Akihiro Seki, Yoshio Sakai, Takuya Komura, Mami Higashimoto, Haruo Fujinaga, Masao Honda, Takashi Wada, Toshinari Takamura, Takahiro Ochiya, Shuichi Kaneko
  • Organizer: The 63rd Annual Meeting of the American Association for the Study Liver Diseases
  • Place of Presentation: BOSTON、アメリカ合衆国