Yuji Teramura1, Hiroo Iwata. 1. Department of Nano-Medicine Merger Education Unit, Graduate School of Engineering, Kyoto University, Kyoto, Japan. teramura@frontier.kyoto-u.ac.jp
Abstract
BACKGROUND: Transplantation of islets of Langerhans (islets) is a promising technique for treating insulin-dependent diabetes mellitus (type I). One unsolved issue is the early graft loss due to inflammatory reactions triggered by blood coagulation and complement activation that occurs immediately after transplantation into the liver through the portal vein. Several proposed approaches for improvement of the graft survival include heparin coating and covalent poly(ethylene glycol) (PEG) conjugation. We previously have studied the improvement of graft survival by modification of islet surfaces using amphiphilic PEG-conjugated phospholipid and bioactive molecules. Here, we analyzed the effect of PEG-modification on the improvement of graft survival immediately after intraportal transplantation into streptozotocin-induced diabetic mice. METHODS: The surface of hamster islets was modified with PEG-lipid. PEG-lipid modified islets (PEG-islets) were transplanted into the liver through the portal vein of streptozotocin-induced diabetic mice. We measured the graft survival periods and blood insulin levels immediately after intraportal transplantation to determine the cell damage to islets. Histocytochemical analyses of liver were also performed postintraportal transplantation. RESULTS: The graft survival of PEG-islets was significantly prolonged compared with bare islets in livers of diabetic mice. Reduction of blood insulin level within 60 min after transplantation of PEG-islets suggests that the cell damage observed immediately after transplantation could be suppressed by surface modification with PEG in comparison with bare islets. CONCLUSION: Our approach for the improvement of graft survival will be useful in the clinical setting.
BACKGROUND: Transplantation of islets of Langerhans (islets) is a promising technique for treating insulin-dependent diabetes mellitus (type I). One unsolved issue is the early graft loss due to inflammatory reactions triggered by blood coagulation and complement activation that occurs immediately after transplantation into the liver through the portal vein. Several proposed approaches for improvement of the graft survival include heparin coating and covalent poly(ethylene glycol) (PEG) conjugation. We previously have studied the improvement of graft survival by modification of islet surfaces using amphiphilic PEG-conjugated phospholipid and bioactive molecules. Here, we analyzed the effect of PEG-modification on the improvement of graft survival immediately after intraportal transplantation into streptozotocin-induced diabeticmice. METHODS: The surface of hamsterislets was modified with PEG-lipid. PEG-lipid modified islets (PEG-islets) were transplanted into the liver through the portal vein of streptozotocin-induced diabeticmice. We measured the graft survival periods and blood insulin levels immediately after intraportal transplantation to determine the cell damage to islets. Histocytochemical analyses of liver were also performed postintraportal transplantation. RESULTS: The graft survival of PEG-islets was significantly prolonged compared with bare islets in livers of diabeticmice. Reduction of blood insulin level within 60 min after transplantation of PEG-islets suggests that the cell damage observed immediately after transplantation could be suppressed by surface modification with PEG in comparison with bare islets. CONCLUSION: Our approach for the improvement of graft survival will be useful in the clinical setting.
Authors: Alexander U Ernst; Daniel T Bowers; Long-Hai Wang; Kaavian Shariati; Mitchell D Plesser; Natalie K Brown; Tigran Mehrabyan; Minglin Ma Journal: Adv Drug Deliv Rev Date: 2019-02-02 Impact factor: 15.470