The journey of islet cell transplantation and future development

Abstract

Intraportal islet transplantation has proven to be efficacious in preventing severe hypoglycemia and restoring insulin independence in selected patients with type 1 diabetes. Multiple islet infusions are often required to achieve and maintain insulin independence. Many challenges remain in clinical islet transplantation, including substantial islet cell loss early and late after islet infusion. Contributions to graft loss include the instant blood-mediated inflammatory reaction, potent host auto- and alloimmune responses, and beta cell toxicity from immunosuppressive agents. Protective strategies are being tested to circumvent several of these events including exploration of alternative transplantation sites, stem cell-derived insulin producing cell therapies, co-transplantation with mesenchymal stem cells or exploration of novel immune protective agents. Herein, we provide a brief introduction and history of islet cell transplantation, limitations associated with this procedure and methods to alleviate islet cell loss as a means to improve engraftment outcomes.

Keywords: immunosuppression; islet engraftment; islet transplantation; mesenchymal stem cells; pluripotent; type 1 diabetes; β cells.

Figure 1.

Drawbacks of islet transplantation. Islet transplantation is a temperate alleviation from exogenous insulin injections. Drawbacks include, but not limited to failed engraftment, the need for a lifelong immunosuppressant therapy, and scarce donor supply. Displayed in colors are possible avenues to help alleviate these drawbacks.

Figure 2.

Mesenchymal stem cell differentiation and co-transplantation. The benefits of MSCs effectiveness to ameliorate islet cell transplantation and MSCs capability to differentiate is displayed. The multipotent capability of MSC can differentiate into mesodermal lineages such as adipocytes, osteocytes, myocytes, and chondrocytes. MSCs co-transplanted with pancreatic islets can decrease the proliferation of natural killer cells, dendritic cells, monocytes, B cells and T cells. The inhibition of T cells promotes regulatory T cells (Tregs). Alongside, MSCs release trophic factors that can improve islet engraftment.