The potential of novel small inhibitory molecules to prevent the rejection of neonatal porcine islets in mice
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Abstract
The objectives of this study were to determine the effect of small inhibitory molecules suramin and DR80 on T cell proliferation in vitro as well as in vivo by preventing the rejection of neonatal porcine islets (NPI) in mice when combined with anti-LFA-1 monoclonal antibody (mAb). Suramin and DR80 inhibited T cell proliferation in vitro in a dose dependent manner with minimal cytotoxicity. As a monotherapy, neither suramin, DR80, nor anti-LFA-1 mAb prevented the rejection of NPI transplants. One of seven mouse recipients treated with suramin and anti-LFA-1 mAb and 6/10 mouse recipients treated with DR80 and anti-LFA-1 mAb achieved normoglycemia for more than 100 days after transplantation; 1 of the mice in the latter group subsequently rejected the NPI transplant. In conclusion, our findings indicates that the combination of DR80 and anti-LFA-1 mAb may be a promising therapy to prevent rejection of NPI in individuals with type 1 diabetes.