Investigation of Differences in Subcutaneous and Liver Surface Transplantation Outcomes and Immune Responses in Islet Adipose-Derived Stem Cell Sheets

2023 Fiscal Year Final Research Report

• Project/Area Number: 19K23608
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0403:Biomedical engineering and related fields
• Research Institution: Nagasaki University
• Principal Investigator: Ikeda Takahiro 長崎大学, 医歯薬学総合研究科(医学系), 研究協力員 (60849511)
• Project Period (FY): 2019-08-30 – 2024-03-31
• Keywords: 膵島/脂肪由来幹細胞複合シート / 膵島 / 脂肪由来幹細胞 / 1型糖尿病 / 移植

Outline of Final Research Achievements

The usefulness of liver surface transplantation was reported in the case of a single islet sheet using cell sheet engineering, rather than subcutaneous transplantation.We expected that islet/ADSC sheets would improve glucose tolerance as much as liver surface transplantation even with less invasive subcutaneous transplantation due to their angiogenesis-inducing/islet cell-protecting effects.
After preparing diabetic model mice and stabilizing the techniques for co-culture sheet preparation and isolation of rat islets, we started islet/ADSC sheet preparation. Five days prior to islet isolation, ADSCs were seeded and grown, islets were isolated, and rat islets were seeded for islet/ADSC sheet preparation. The islet/ADSC sheets were continuously transplanted into diabetic mice, but they did not grow well and showed no hypoglycemic effect.

Free Research Field

移植外科学

Academic Significance and Societal Importance of the Research Achievements

既存の1型糖尿病に対する移植治療には膵臓移植と膵島移植があるが、克服すべき課題も多い。膵臓移植にはドナー不足、高い侵襲性の問題があり、膵島移植には経門脈移植による塞栓の危惧、移植量の制限、生着に至るまでの膵島消失、低いインスリン離脱率などの問題がある。そのため低侵襲で治療効果の高い移植方法の確立が望まれる。膵島/脂肪由来幹細胞複合シートには血管新生誘導、膵島保護効果により高い生着率・移植成績を認めつつ、低侵襲な治療法となる可能性を秘めている。今回、非免疫抑制マウスを用いることでADSCのもつ免疫回避能にも期待したが生着しなかった。免疫抑制マウスを用いれば、耐糖能改善に寄与できた可能性がある。