Abstract
BackgroundPancreatic islet encapsulation is one way to address the disadvantages of islet transplantation. Not only does encapsulation involve bidirectional diffusion of nutrients, oxygen, and glucose, but also it protects the graft from the recipient’s immune reaction. The high mobility group box 1 (HMGB1), one of higher expression proteins in islet, can be secreted from transplanted islets and induce the inflammation. Therefore, the regulation of HMGB1-mediated inflammation is very important for successful islet transplantation. In this study, we used the HMGB1 A box, an antagonist of HMGB1 receptor in the immune cells, in the encapsulation of isolated islets as a new strategy.ResultFor co-encapsulation of HMGB1 A box protein with islets, we evaluated the distribution of alginate bead diameter. The average diameter of empty alginate bead was similar to that of alginate bead with islets. When different concentrations of HMGB1 A box protein was co-encapsulated with islets, it did not affect the viability and insulin secretion function of the islets. When the alginate beads with islets plus HMGB1 A box protein were cultured with macrophage, the amount of TNF-α secreted from the macrophages was significantly attenuated when compared to cultivation of unencapsulated islets or encapsulated islets. When the alginate beads with islets plus HMGB1 A box protein were intraperitoneally xenotransplanted into the diabetic mice, the survival rate of the islets was strongly improved with 2-fold.ConclusionCollectively, these results suggested that the encapsulation of HMGB1 A box protein might offer a protective effect in islet transplantation.
Highlights
Pancreatic islet encapsulation is one way to address the disadvantages of islet transplantation
Collectively, these results suggested that the encapsulation of high mobility group box 1 (HMGB1) A box protein might offer a protective effect in islet transplantation
The isletcontaining alginate beads were uniform with a polydistribution index (PDI) of ±1.08
Summary
Type 1 Diabetes Mellitus (T1DM) is chronic disease that results from the autoreactive T lymphocyte-mediated destruction of beta cells in the pancreatic islets of Langerhans [1]. This autoimmune cell destruction against islets leads to a deficiency of insulin hormone in the body. There have been many prior attempts to overcome the disadvantages islet transplantation, including especially pancreatic islet encapsulation with alginate hydrogel. This islet encapsulation remedy may remove the need for immunosuppressive drugs because the alginate bead could inhibit the recognition of host’s immune cells through ‘immune-isolation’, thereby reducing the inflammation [6, 7]. Alginate bead can allow the bidirectional diffusion of nutrients, oxygen, and glucose to the
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