HMGB1 매개성 염증반응 억제형 췌장소도 피막화 연구

Abstract

Insulin-secreting pancreatic islet transplantation is a promising treatment for diabetes mellitus. However, one technical challenge is attenuation of early graft loss after islet transplantation. For that reason, to overcome disadvantage of islet transplantation, pancreatic islet encapsulation is being tried over the past century. Also, islet encapsulation could bidirectional diffusion of nutrients, oxygen, and glucose. However, this islet encapsulation has limitation such as hypoxia damage. Recently, it was reported that a high mobility group box 1 (HMGB1) is overexpressed in pancreatic islet cells, which is one of important candidate for early loss of islets. In general, HMGB1 acts as a trigger of inflammation, attracting inflammatory cells such as macrophage and dendritic cell. HMGB1 is a chromosomal protein composed of two DNA-binding domains (A box and B box) and an acidic C-terminal tail. Among them, HMGB1 A box has a characteristic that antagonized inflammation-inducing activity of HMGB1. Therefore, here we separately cloned and expressed the HMGB1A protein to attenuate the early graft loss using alginate bead with islet. To this end, this HMGB1 A box was only inside or outside the alginate bead for its controlled release. First, we confirmed that morphology and size distribution of alginate beads. In addition, confirmed that viability of HMGB1 treated to islets and encapsulated islet with HMGB1 A box. Functional test of encapsulated islet with HMGB1 A box was measured. To evaluate the effects of encapsulated islet with HMGB1 A box in vivo, xeno-transplanted the encapsulated islet and encapsulated islet with HMGB1 A box (1000 islets per mouse) into peritoneal cavity in the streptozotocin-induced diabetic balb/c mice. Collectively, these results that encapsulated islet with HMGB1 A box would delay the early graft loss from immune reaction in islet xenotransplantation. To clearly evaluate effect of this system, we are ongoing in vivo and in vitro studies.