Development of stem cell therapy for colitis and colitis-associated carcinogenesis

• Project/Area Number: 21590819
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Sapporo Medical University
• Principal Investigator: ARIMURA Yoshiaki 札幌医科大学, 医学部, 講師 (80305218)
• Co-Investigator(Kenkyū-buntansha): MOTOYA Masayo (HOSOKAWA Masayo) 札幌医科大学, オホーツク医療環境研究講座, 特任助教 (60468080)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2011: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2010: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2009: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 下部消化管学(小腸,大腸) / 骨髄間葉系幹細胞(MSC) / MSC馴化培地(MSC-CM) / 低酸素 / 炎症発癌 / 腸上皮細胞 / タイトジャンクション / 血管新生 / 筋原細胞

Research Abstract

The therapeutic action of MSC remains to be clarified although mesenchymal stem cell(MSC) therapy was effective for rodent experimental colitis with low engraftment. Paracrine effects with pleiotropic gut trophic factors identified in the MSC conditioned medium were paramount importance as for its therapeutic action. MSC promoted xenografting tumor proliferation with MSC-dependent angiogenesis while MSC partially cancel azoxymethane-induced tumor initiation in systemic administration.

Research Products

• [Journal Article] Regenerative medicine for inflammatory bowel disease (2012)
  • Author(s): Yoshiaki Arimura
  • Journal Title: Inflammation and Regeneration Volume: 32 Pages: 61-66
  • NAID: 130004482295
• [Journal Article] Dynamics of claudins expression in colitis and colitis-associated cancer in rat (2011)
  • Author(s): Arimura Y, Nagaishi K, Hosokawa M
  • Journal Title: Methods Mol Biol Volume: 762 Pages: 409-425
• [Journal Article] The efficacy of IGF-I receptor monoclonal antibody against human gastrointestinal carcinomas is independent of k-ras mutation status (2011)
  • Author(s): Ii M, Li H, Adachi Y, Yamamoto H, Ohashi H, Taniguchi H, Arimura Y, Carbone DP, Imai K, Shinomura Y
  • Journal Title: Clin Cancer Res Volume: 17 Pages: 5048-5059
  • Peer Reviewed
• [Journal Article] Myogenic lineage differentiated mesenchymal stem cells enhance recovery from dextran sulfate sodium-induced colitis in the rat (2011)
  • Author(s): Tanaka H, Arimura Y, Yabana T, Goto A, Hosokawa M, Nagaishi K, Yamashita K, Yamamoto H, Sasaki Y, Fujimiya M, Imai K, Shinomura Y
  • Journal Title: J Gastroenterol Volume: 46 Pages: 143-152
  • NAID: 10029027000
  • Peer Reviewed
• [Journal Article] Dynamics of claudins expression in colitis and colitis-associated cancerin rat (2011)
  • Author(s): Yoshiaki Arimura
  • Journal Title: Methods Mol Biol Volume: 762 Pages: 409-425
  • DOI: 10.1007/978-1-61779-185-7_29
  • ISBN: 9781617791840, 9781617791857
• [Journal Article] A genome-wide association study identifies three new susceptibility loci for ulcerative colitis in the Japanese population (2009)
  • Author(s): Asano K, Matsushita T, Umeno J, Hosono N, Takahashi A, Kawaguchi T, Matsumoto T, Matsui T, Kakuta Y, Kinouchi Y, Shimosegawa T, Hosokawa M, Arimura Y, Shinomura Y, Kiyohara Y, Tsunoda T, Kamatani N, Iida M, Nakamura Y, Kubo M
  • Journal Title: Nat Genet Volume: 41 Pages: 1325-1329
  • Peer Reviewed
• [Journal Article] Genetic variants in surfactant, pulmonary-associated protein D(SFTPD) and Japanese susceptibility to ulcerative colitis (2009)
  • Author(s): Tanaka M, Arimura Y, Goto A, Hosokawa M, Nagaishi K, Yamashita K, Yamamoto H, Sonoda T, Nomura M, Motoya S, Imai K, Shinomura Y
  • Journal Title: Inflamm Bowel Dis Volume: 15 Pages: 918-925
  • Peer Reviewed
• [Journal Article] Enhancing epithelial engraftment of rat mesenchymal stem cells restores epithelial barrier integrity (2009)
  • Author(s): Yabana T, Arimura Y, Tanaka H, Goto A, Tanaka M, Hosokawa M, Nagaishi K, Yamashita K, Yamamoto H, Adachi Y, Isobe M, Fujimiya M, Imai K, Shinomura Y
  • Journal Title: J Pathol Volume: 218 Pages: 350-359
  • Peer Reviewed
• [Journal Article] A genome-wide association study identifies three new susceptibility loci for ulcerative colitis in the Japanese population (2009)
  • Author(s): Asano K
  • Journal Title: Nat Genet 41 Pages: 1325-1329
  • Peer Reviewed
• [Journal Article] Enhancing epithelial engraftment of rat mesenchymal stem cells restores epithelial barrier integrity (2009)
  • Author(s): Yabana T
  • Journal Title: J Pathol 218 Pages: 350-359
  • Peer Reviewed
• [Journal Article] Genetic variants in surfactant, pulmonary-associated protein D(SFTPD)and Japanese susceptibility to ulcerative colitis (2009)
  • Author(s): Tanaka M
  • Journal Title: Inflamm Bowel Dis 15 Pages: 918-925
  • Peer Reviewed
• [Journal Article] Pathology and pathophysiology of inflammatory bowel diseases.2.Genetic background (2009)
  • Author(s): Watanabe S
  • Journal Title: Nippon Naika Gakkai Zasshi 98 Pages: 18-24
• [Journal Article] ゲノムワイド関連解析により10番染色体短腕12.2にサルコイドーシスおよびクローン病に共通の疾患感受性遺伝子座が存在する (2009)
  • Author(s): 有村佳昭
  • Journal Title: Review of Gastroenterology & Clinical Gastroenterology and Hepatology 4 Pages: 33-38
• [Presentation] Pleiotropic action of gut tropic factors derived from conditioned mesenchymal stem cells (2012)
  • Author(s): Kanna Nagaishi
  • Organizer: 6th Japan-Korea IBD Symposium
  • Place of Presentation: 東京
  • Year and Date: 2012-01-28
• [Presentation] 骨髄間葉系幹細胞由来Gut Trophic Factorはラット実験腸炎の回復を促進する (2011)
  • Author(s): 渡邊秀平, 有村佳昭, 永石歓和, 那須野正尚, 篠村恭久
  • Organizer: 第53回日本消化器病学会大会
  • Place of Presentation: 福岡
  • Year and Date: 2011-10-20
• [Presentation] MSC由来Gut trophic factorのラットDSS腸炎における役割 (2011)
  • Author(s): 永石歓和, 渡邊秀平, 那須野正尚, 苗代康可, 有村佳昭, 篠村恭久
  • Organizer: 第48回日本消化器免疫学会総会
  • Place of Presentation: 金沢
  • Year and Date: 2011-07-21
• [Presentation] Reciprocal relation between MSC-dependent angiogenesis and VEGF expression in colorectal cancer (2011)
  • Author(s): Kanna Nagaishi, Yoshiaki Arimura, Masanao Nasuno, Yasuhisa Shinomura
  • Organizer: DDW2011
  • Place of Presentation: Chicago
  • Year and Date: 2011-05-10
• [Presentation] Reciprocal relation between tumor angiogenesis and MSC-dependent growth in colorectal cancer (2011)
  • Author(s): Kanna Nagaishi, Yoshiaki Arimura, Daisuke Suzuki, Koji Ataka, Yasuhisa Shinomura, Mineko Fujimiya
  • Organizer: 第116回日本解剖学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2011-03-30
• [Presentation] Pleiotropic Action of Gut Tropic Factors Derived from Conditioned Mesenchymal Stem Cells (2011)
  • Author(s): Kanna Nagaishi, Shuhei Watanabe, Yasuyoshi Naishiro, Kentaro Yamashita, Yoshiaki Arimura, Mineko Fujimiya, Yasuhisa Shinomura, Kohzoh Imai
  • Organizer: 6th Japan-Korea IBD Symposium
  • Place of Presentation: Tokyo
  • Year and Date: 2011-01-28
• [Presentation] 骨髄間葉系幹細胞(MSC)は大腸癌細胞の生着を促進させる-腫瘍細胞のVEGF発現とMSC依存性増殖の関連- (2010)
  • Author(s): 中垣卓
  • Organizer: JDDW2010
  • Place of Presentation: 横浜
  • Year and Date: 2010-10-14
• [Presentation] Reciprocal relation tumor angiogenesis with MSC-dependent growth in colorectal cancer cell lines xenograft (2010)
  • Author(s): Nasuno M, Arimura Y, Nakagaki S, Watanabe S, Nagaishi K, Naishiro Y, Imai K, Shinomura Y
  • Organizer: 5th Korea-Japan IBD Symposium
  • Place of Presentation: Seoul
  • Year and Date: 2010-10-02
• [Presentation] Reciprocal relation tumor angiogenesis with MSC-dependent growth in colorectal cell lines xenograft (2010)
  • Author(s): Nasuno M
  • Organizer: The 5th Korea-Japan Inflammatory Bowel Disease Symposium
  • Place of Presentation: Seoul
  • Year and Date: 2010-10-02
• [Presentation] Enhancing mucosal reparative response in rat DSS colitis by mesenchymal stem cell therapy (2010)
  • Author(s): Tanaka H, Arimura Y, Yabana T, Goto A, Hosokawa M, Nagaishi K, Naishiro Y, Yamashita K, Yamamoto H, Murata M, Fujimiya M, Imai K, Shinomura Y
  • Organizer: 4th Korea-Japan IBD Symposium
  • Place of Presentation: Tokyo
  • Year and Date: 2010-01-23
• [Presentation] Enhancing mucosal reparative response in rat DSS colitis by Mesenchymal Stem Cell therapy (2010)
  • Author(s): Tanaka H
  • Organizer: The 4th Korea-Japan Inflammatory Bowel Disease Symposium
  • Place of Presentation: 東京
  • Year and Date: 2010-01-23
• [Book] 炎症性腸疾患.病因解明と診断・治療の最新知見.,炎症性腸疾患における発癌機序 (2012)
  • Author(s): 渡邊秀平, 有村佳昭, 今井浩三
  • Publisher: 日本臨床社
• [Book] 炎症性腸疾患-病因解明と診断・治療の最新知見(炎症性腸疾患における発癌機序) (2012)
  • Author(s): 渡邊秀平
  • Publisher: 日本臨床社
• [Book] IBD(炎症性腸疾患)を究める, II.炎症性腸疾患の病因・病態組織修復・再生 (2011)
  • Author(s): 那須野正尚, 有村佳昭, 今井浩三
  • Publisher: メジカルビュー社
• [Book] IBD(炎症性腸疾患)を究める(II.炎症性腸疾患の病因・病態 組織修復・再生) (2011)
  • Author(s): 那須野正尚
  • Publisher: メジカルビュー社
• [Book] 炎症性腸疾患(X 炎症性腸疾患における癌化機序) (2010)
  • Author(s): 那須野正尚
  • Publisher: 医学書院
• [Book] 大腸疾患NOW(腸炎関連発癌におけるMSCの役割) (2010)
  • Author(s): 有村佳昭
  • Publisher: 日本メディカルセンター
• [Book] 日本内科学会雑誌, II.炎症性腸疾患の病理・病態生理3.遺伝的背景 (2009)
  • Author(s): 渡邊修平, 有村佳昭, 細川雅代, 田中浩紀, 篠村恭久, 今井浩三
  • Publisher: 日本内科学会
• [Book] 大腸疾患NOW2009,第二部炎症性腸疾患をめぐる最近の話題5.炎症と発癌における骨髄の役割 (2009)
  • Author(s): 中垣卓, 細川雅代, 有村佳昭
  • Publisher: 日本メディカルセンター
• [Book] 大腸疾患NOW 2009 (2009)
  • Author(s): 中垣卓
  • Total Pages: 223
  • Publisher: 日本メディカルセンター
• [Remarks]
  • URL: http://web.sapmed.ac.jp/im1/SubPage/04_Kenkyu/Kaisetsu02.html
• [Remarks]
  • URL: http://web.sapmed.ac.jp/im1/SubPage/04_Kenkyu/Kaisetsu02.html
• [Remarks]
  • URL: http://web.sapmed.ac.jp/im1/SubPage/04_Kenkyu/Kaisetsu02.html
• [Remarks]
  • URL: http://www.sapmed.ac.jp/im1/SubPage/04_Kenkyu/Kaisetsu02.html
• [Patent(Industrial Property Rights)] 間葉系幹細胞(MSC)の培養上清を含む腸炎の予防・治療剤。 (2011)
  • Inventor(s): 有村佳昭,永石歓和,渡邊秀平
  • Industrial Property Rights Holder: 札幌医科大学
  • Filing Date: 2011-07-13
• [Patent(Industrial Property Rights)] 間葉系幹細胞(MSC)の培養上清を含む腸炎の予防・治療剤 (2011)
  • Inventor(s): 有村佳昭
  • Industrial Property Rights Holder: 札幌医科大学
  • Filing Date: 2011-07-13