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Encapsulation of pancreatic islet with HMGB1 fragment for attenuating inflammation

  • Jo, Eun Hee (Department of Bioengineering, College of Engineering, Hanyang University) ;
  • Hwang, Yong Hwa (Department of Bioengineering, College of Engineering, Hanyang University) ;
  • Lee, Dong Yun (Department of Bioengineering, College of Engineering, Hanyang University)
  • 투고 : 2015.09.01
  • 심사 : 2015.10.01
  • 발행 : 2015.12.31

초록

Background: Pancreatic 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. Result: For 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 $TNF-{\alpha}$ 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. Conclusion: Collectively, these results suggested that the encapsulation of HMGB1 A box protein might offer a protective effect in islet transplantation.

키워드

과제정보

연구 과제 주관 기관 : National Research Foundation of Korea (NRF)

참고문헌

  1. Pavlakis M, Khwaja K. Pancreas and islet cell transplantation in diabetes. Curr Opin Endocrinol Diabetes Obes. 2007;14:146-50. https://doi.org/10.1097/MED.0b013e32807f2ac8
  2. Ricordi C, Strom TB. Clinical islet transplantation: advances and immunological challenges. Nat Rev Immunol. 2004;4:259-68. https://doi.org/10.1038/nri1332
  3. Kelly WD, Lillehei RC, Merkel FK, Idezuki Y, Goetz FC. Allotransplantation of the pancreas and duodenum along with the kidney in diabetic nephropathy. Surgery. 1967;61:827-37.
  4. Boker A, Rothenberg L, Hernandez C, Kenyon NS, Ricordi C, Alejandro R. Human islet transplantation: Update. World J Surg. 2001;25:481-86. https://doi.org/10.1007/s002680020341
  5. Shapiro AMJ, Lakey JRT, Ryan EA, Korbutt GS, Toth E, Warnock GL, et al. Islet transplantation in seven patients with type 1 diabetes mellitus using a glucocorticoid-free immunosuppressive regimen. New England Journal of Medicine. 2000;343:230-38. https://doi.org/10.1056/NEJM200007273430401
  6. Kizilel S, Garfinkel M, Opara E. The bioartificial pancreas: progress and challenges. Diabetes Technol Ther. 2005;7:968-85. https://doi.org/10.1089/dia.2005.7.968
  7. Opara EC, Kendall Jr WF. Immunoisolation techniques for islet cell transplantation. Expert Opin Biol Ther. 2002;2:503-11. https://doi.org/10.1517/14712598.2.5.503
  8. Lim F, Sun AM. Microencapsulated Islets as Bioartificial Endocrine Pancreas. Science. 1980;210:908-10. https://doi.org/10.1126/science.6776628
  9. Grose S. Critics slam Russian trial to test pig pancreas for diabetics. Nat Med. 2007;13:390-1.
  10. de Vos P, Hamel AF, Tatarkiewicz K. Considerations for successful transplantation of encapsulated pancreatic islets. Diabetologia. 2002;45:159-73. https://doi.org/10.1007/s00125-001-0729-x
  11. de Groot M, Schuurs TA, Keizer PP, Fekken S, Leuvenink HG, van Schilfgaarde R. Response of encapsulated rat pancreatic islets to hypoxia. Cell Transplant. 2003;12:867-75. https://doi.org/10.3727/000000003771000219
  12. Hals IK, Rokstad AM, Strand BL, Oberholzer J, Grill V. Alginate Microencapsulation of Human Islets Does Not Increase Susceptibility to Acute Hypoxia. Journal of Diabetes Research. 2013;2013:9.
  13. Lotze MT, Tracey KJ. High-mobility group box 1 protein (HMGB1): nuclear weapon in the immune arsenal. Nat Rev Immunol. 2005;5:331-42. https://doi.org/10.1038/nri1594
  14. Yang H, Wang HC, Czura CJ, Tracey KJ. HMGB1 as a cytokine and therapeutic target. J Endotoxin Res. 2002;8:469-72. https://doi.org/10.1179/096805102125001091
  15. Harris HE, Andersson U, Pisetsky DS. HMGB1: a multifunctional alarmin driving autoimmune and inflammatory disease. Nat Rev Rheumatol. 2012;8:195-202. https://doi.org/10.1038/nrrheum.2011.222
  16. Matsuoka N, Itoh T, Watarai H, Sekine-Kondo E, Nagata N, Kamoto K, et al. High-mobility group box 1 is involved in the initial events of early loss of transplanted islets in mice. Journal of Clinical Investigation. 2010;120:735-43. https://doi.org/10.1172/JCI41360
  17. Harris HE, Andersson U. The nuclear protein HMGB1 as a proinflammatory mediator. Eur J Immunol. 2004;34:1503-12. https://doi.org/10.1002/eji.200424916
  18. Itoh T, Iwahashi S, Shimoda M, Chujo D, Takita M, SoRelle JA, et al. High-mobility group box 1 expressions in hypoxia-induced damaged mouse islets. Transplant Proc. 2011;43:3156-60. https://doi.org/10.1016/j.transproceed.2011.09.100

피인용 문헌

  1. The Role of HMGB1 in the Pathogenesis of Type 2 Diabetes vol.2016, pp.None, 2015, https://doi.org/10.1155/2016/2543268
  2. Islet‐derived damage‐associated molecular pattern molecule contributes to immune responses following microencapsulated neonatal porcine islet xenotransplantation in mice vol.23, pp.5, 2015, https://doi.org/10.1111/xen.12253
  3. Vitexin alleviates lipopolysaccharide-induced islet cell injury by inhibiting HMGB1 release vol.15, pp.3, 2015, https://doi.org/10.3892/mmr.2017.6114
  4. The intraperitoneal space is more favorable than the subcutaneous one for transplanting alginate fiber containing iPS-derived islet-like cells vol.11, pp.None, 2015, https://doi.org/10.1016/j.reth.2019.05.003
  5. The effect of preexisting HMGB1 within fetal bovine serum on murine pancreatic beta cell biology vol.12, pp.1, 2015, https://doi.org/10.1080/19382014.2019.1696128