Advancements in innate immune regulation strategies in islet transplantation

Abstract

As a newly emerging organ transplantation technique, islet transplantation has shown the advantages of minimal trauma and high safety since it was first carried out. The proposal of the Edmonton protocol, which has been widely applied, was a breakthrough in this method. However, direct contact between islets and portal vein blood will cause a robust innate immune response leading to massive apoptosis of the graft, and macrophages play an essential role in the innate immune response. Therefore, therapeutic strategies targeting macrophages in the innate immune response have become a popular research topic in recent years. This paper will summarize and analyze recent research on strategies for regulating innate immunity, primarily focusing on macrophages, in the field of islet transplantation, including drug therapy, optimization of islet preparation process, islet engineering and Mesenchymal stem cells cotransplantation. We also expounded the heterogeneity, plasticity and activation mechanism of macrophages in islet transplantation, providing a theoretical basis for further research.

Strategy for Clinical Setting of Co-transplantation of Mesenchymal Stem Cells and Pancreatic Islets

“…MSCs act on T cells by physically hindering the contact of antigen-presenting cells or through intercellular contacts hindering dendritic cells’ maturation indirectly inhibiting T-cell activation. Moreover, MSCs are able to inhibit T-cell reactivity and evade cytotoxic T-cell-mediated apoptosis via soluble factors such as transforming growth factor b1 and hepatic growth factor or nitric oxide and downregulation of pro-inflammatory cytokines 42 . Among these, transforming growth factor b1 plays a full role in immunomodulation of MSCs, including a role in regulatory cell induction and/or expansion 43 .…”