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P.119 Evaluation of the transplant site environment in prevascularized subcutaneous islet transplantation

Takayuki Anazawa, Japan

Assistant Professor
Surgery
Kyoto University

Abstract

Evaluation of the transplant site environment in prevascularized subcutaneous islet transplantation

Takayuki Anazawa1, Kenta Inoguchi1, Norio Emoto1, Nanae Fujimoto1, Kei Yamane1, Seiichiro Tada1, Koichiro Hata1, Toshihiko Masui1, Kojiro Taura1, Etsuro Hatano1.

1Surgery, Kyoto University, Kyoto, Japan

Introduction: The subcutaneous site is a promising transplantation site because it is possible to monitor and remove the graft to ensure safety for the clinical application of islet-like cells derived from ES/iPS cells. It is required to induce a vascular bed in advance, but the optimal conditions for this are unclear. We evaluated the immunological environment of the transplantation site after prevascularization.

Method: 500 islets of C57BL/6 mice were transplanted into the prevascularized subcutaneous site of C57BL/6 mice by implanting agarose rods with bFGF. The agarose rod implantation period was set at 7 days and 14 days, and the blood glucose levels, cell infiltration, and cytokines before transplantation were evaluated. We also evaluated the transplant results when anti-TNF antibody was used.

Results: The 14-day group showed early glycemic normalization (At 30 days post-transplantation: 17% in the 7-day group, 83% in the 14-day group; At 40 days: 67% in the 7-day group, 83% in the 14-day group). The 14-day group showed numerous macrophage accumulation at the transplant site (7-day group: 7.8%; 14-day group: 24%; p = [Editor1] 0.03). The ratio of macrophage 1 to macrophage 2 was higher in the 7-day group (2.12 in the 7-day group; 0.10 in the 14-day group; p = 0.001), and IL-6 and TNF were locally higher at the transplant site (273 pg/mL in the 7-day group; 48.4 pg/mL in the 14-day group; p = 0.04, 40 pg/mL in the 7-day group for TNF; 14 pg/mL in the 14-day group for IL-6). The use of anti-TNF antibody in the 7-day group resulted in early glycemic normalization (glycemic normalization rate at 30 days after transplantation: 83%).

Conclusion: In the early stage of the prevascularization before subcutaneous transplantation, the accumulation of macrophage 1 prevented early engraftment due to the production of inflammatory cytokines. For clinical application, it is necessary to explore the optimal setting of the transplantation environment after prevascularization.