Establishment of hereditary pancreatitis patient-derived iPS cells

• Project/Area Number: 16K15421
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Gastroenterology
• Research Institution: Tohoku University
• Principal Investigator: Masamune Atsushi 東北大学, 医学系研究科, 教授 (90312579)
• Co-Investigator(Kenkyū-buntansha): 濱田 晋 東北大学, 医学系研究科, 助教 (20451560) ; 児玉 裕三 神戸大学, 医学研究科, 教授 (80378687) ; 長船 健二 京都大学, iPS細胞研究所, 教授 (80502947)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: 遺伝性膵炎 / iPS細胞

Outline of Final Research Achievements

The purpose of the current study is to establish iPS cells from patients with gene mutation related to chronic pancreatitis. In addition, we tried to establish a novel protocol to differentiate iPS cells into mature pancreatic acinar cells. We obtained peripheral blood mononuclear cells from blood samples of patients who agreed participation, with a written informed consent. Introduction of Yamanaka factors led to the formation of iPS cells in all of the patients. Established iPS cells were cultured and stored for further usage. A novel differentiation protocol using small molecule agents was established by the 2D-culture based drug screening. This protocol induced acinar cell marker, such as amylase, in iPS cells. However, final differentiation protocol into mature acinar cells has not yet been established. The current study enabled iPS cell library from patients with pancreatitis caused by genetic burden.

Academic Significance and Societal Importance of the Research Achievements

本研究は指定難病でもある遺伝性膵炎を含め、遺伝的素因により発症する膵炎患者においてiPS細胞を作成し、機能解析に供することのできる基盤形成につながった。通常の検査に附随して得られる末梢血検体からの樹立が可能であり、施設間連携の点からも疾患特異的iPS細胞樹立のためのモデルの一つになりうると考えられる。既知遺伝子のみならず、原因遺伝子が不明なケースについてもiPS細胞化により将来の解析に備えることが可能となった点は意義深い。

Research Products

• [Journal Article] Protease-Sensitive Pancreatic Lipase Variants Are Associated With Early Onset Chronic Pancreatitis. (2019)
  • Author(s): Lasher D, Szabo A, Masamune A, Chen JM, Xiao X, Whitcomb DC, Barmada MM, Ewers M, Ruffert C, Paliwal S, Issarapu P, Bhaskar S, Mani KR, Chandak GR, Laumen H, Masson E, Kume K, Hamada S, Nakano E, Seltsam K, Bugert P, Muller T, Groneberg DA, Shimosegawa T, Rosendahl J, Ferec C, Lowe ME, Witt H, Sahin-Toth M.
  • Journal Title: Am J Gastroenterol. Volume: - Issue: 6 Pages: 974-983
  • DOI: 10.14309/ajg.0000000000000051
  • Peer Reviewed / Int'l Joint Research