Treatment of DSS colitis with MSCs derived from MHC-homozygous iPSCs with using cynomolgus macaque

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K09379
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Shiga University of Medical Science
• Principal Investigator: Ogasawara Kazumasa 滋賀医科大学, 医学部, 教授 (20169163)
• Co-Investigator(Kenkyū-buntansha): 伊藤 靖 滋賀医科大学, 医学部, 教授 (90324566) ; 石垣 宏仁 滋賀医科大学, 医学部, 助教 (90432301)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: DSS colitis / MSC / iPSC / cynomolgus macaque

Outline of Final Research Achievements

Monkey iPS cell-derived mesenchymal stem cells (iMSCs) and monkey bone marrow-derived mesenchymal stem cells (BM-MSCs) were administered to a DSS colitis model of cynomolgus macaque, and the therapeutic effect on colitis was examined endoscopically and histologically. As a result, no therapeutic effect was observed for both iMSC and BM-MSC. Unlike human MSCs, monkey iMSCs and monkey BM-MSCs did not produce IL-10, which is one of anti-inflammatory cytokine. Therefore, iMSC-IL10 in which IL-10 was forcibly expressed in iMSCs were established and administered to treat monkey DSS colitis. Although IL-10 levels were elevated in the peripheral blood of cynomolgus monkeys treated with iMSC-IL10, no improvement in DSS colitis was observed. However, iMSC-IL10 histologically provided slight improvement of the colitis and then we ought to perform further experiments in future.

Free Research Field

Pathology

Academic Significance and Societal Importance of the Research Achievements

1)下剤の投与量と投与タイミングを調整することで、カニクイザル に対し、安定した下部消化管内視鏡を行うことができた。またDSSの投与量を工夫することで、世界で初めてカニクイザルDSS腸炎モデルを作製することができた。
2)iMSC-IL10を作成し、カニクイザルに投与したところ、末梢血中でのIL-10濃度の上昇を認めたことから、iMSCを担体としたcytokine deliver systemの可能性を示すことができた。
3)iMSC-IL10を投与後に、histological scoreにおいて若干の改善を認めたことから、さらなる検討が必要と考えられた。