Poster Presentation The 13th International Congress of the Immunology of Diabetes Society 2013

Immune-suppressive Properties of Human Islet-derived Progenitor Cells (#163)

Mugdha Joglekar 1 , Ammira Akil 2 , Helen Thomas 3 , Anandwardhan Hardikar 1
  1. University of Sydney, Camperdown, NSW, Australia
  2. University of New South Wales, Sydney
  3. St. Vincent's Institute, Fitzroy, Vic, Australia

Transplantation of cadaveric islets is currently the most successful cell-based therapy for treatment of type 1 diabetes. However, long-term success of this therapy is severely limited by multiple factors, including the immune-mediated destruction of transplanted islets. Development of cell-based immunosuppressive strategies could offer better graft survival and function in replacement therapies for diabetes.
We have established and extensively characterized human islet-derived progenitor cells (hIPCs), which are generated following epithelial-to-mesenchymal transition (EMT) and proliferation (expansion) of human cadaveric islets. Initial characterization of hIPCs indicates that they exhibit most of the characteristics of mesenchymal stem cells, including expression of vimentin, CD73, CD90 and CD105. We now report that hIPCs can significantly inhibit in vitro proliferation of different immune cell subsets (CD4+ T, CD8+ T, CD19+ B) of phytohemagglutinin (PHA)-stimulated human peripheral blood mononuclear cells (hPBMCs) in a co-culture system. We observe that this inhibition is most effective when there is direct cell-cell contact, although significant inhibition is also retained in a transwell system. This inhibition of proliferation can be rescued by using methyl tryptophan, an antagonist of indoleamine-pyrrole 2,3-dioxygenase (IDO), indicating a role of IDO in hIPC-mediated immune repression.
Present experiments are focused on understanding the non-codingRNAs and other inhibitory molecules that could be responsible for the immunomodulatory function of hIPCs. We believe that such islet-derived progenitors could offer a novel immunoregulatory approach for improving graft survival in islet transplantation for diabetes.

Authors acknowledge the JDRF post-doctoral award to MJ and infrastructure support by NHMRC-CTC and SVI.