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Acceptance of Murine Islet Allografts Without Immunosuppression in the Inguinal Subcutaneous White Adipose Tissue Pretreated with bFGF

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posted on 23.05.2022, 00:10 authored by Yuki Nakafusa, Naoyoshi Nitta, Kazunari Ishii, Naoto Shirasu, Takahiro Iwamoto, Takayuki Nemoto, Masafumi Nakamura, Masafumi Goto, Hiroo Iwata, Masaru Taniguchi, Yohichi Yasunami

  

Prevention of immune rejection without immunosuppression is the ultimate goal of transplant immunobiology. One way to achieve this in cellular transplantation, such as with islet transplantation, is to create a favorable local environment at the transplant site. In the present study, we found that streptozotocin (STZ)-induced diabetic C57BL/6 mice remained normoglycemic for more than one year after transplantation of BALB/c islets without immunosuppression when the inguinal subcutaneous white adipose tissue (ISWAT) was the site of transplantation and when the site was pretreated with basic fibroblast growth factor. Mechanistically, mesenchymal stem cells (MSCs) expanded in the ISWAT after the treatment was found to produce TGFb and prevention of islet allograft rejection could be achieved by co-transplantation with syngeneic MSCs isolated from the ISWAT after the treatment, which was abolished by anti-TGFb antibody treatment. Importantly, TGFb-producing cells remained present at the site of co-transplantation for up to the end of observation period at 240 days after transplantation. 

These findings indicate that prevention of islet allograft rejection without immunosuppression is feasible with the use of syngeneic TGFb-producing MSCs expanded in the ISWAT after the treatment with bFGF, providing a novel strategy for prevention of islet allograft rejection without immunosuppression. 

Funding

This work was supported by Japan Agency for Medical Research and Development (20bm0404030, YY, MG, HI) and by funds from the Central Research Institute of Fukuoka University (No. 932, YY, TI).

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