Poster Presentation Australian Diabetes Society and the Australian Diabetes Educators Association Annual Scientific Meeting 2014

Human Islet-derived Progenitor Cells regulate T cell proliferation via exosomal transfer of microRNAs (#254)

Mugdha Joglekar 1 , Ammira Akil 2 , Edwin Lim 3 , Gilles Guillemin 3 , Helen Thomas 4 , Anandwardhan Hardikar 1
  1. University of Sydney, Camperdown, NSW, Australia
  2. University of New South Wales, Sydney
  3. Macquarie University, NSW
  4. 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. Bioinformatic analysis of our next generation sequencing data indicates non-coding RNAs to be responsible for the immunomodulatory properties of hIPCs. Studies in understanding the mechanism of transfer of these non-coding RNAs to T-cells are currently underway.  We believe that such islet-derived progenitors offer a novel immunoregulatory approach for improving graft survival in islet transplantation for diabetes.