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Islet surface PEGylation attenuate the instant blood-mediated inflammatory reaction in intrahepatic islet transplantation

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Abstract

Clinically intrahepatic pancreatic islet transplantation is carried out for patients suffering from type 1 diabetes mellitus but the instant blood mediated inflammatory reaction (IBMIR) initiated from platelet adhesion onto the islet can impair the islet function. Previously, chemically modified islets were developed with a protective poly(ethylene glycol) (PEG) polymer, which could repel adhering platelets in the blood stream owing to its biocompatible properties. The results show that PEG-based chemical modification can prevent the adhesion of platelets in the tubing loop model in vitro. Moreover, this islet PEGylation strategy appears to avoid the islet cytotoxicity associated with the further recruitment of leukocytes and monocytes via an interaction with platelets, thereby showing normal viability and function of insulin secretion of the PEGylated islets. In addition, when transplanted into the liver via the portal vein, the PEGylated islets could still normally function for insulin secretion without binding onto the islet surface with platelets and/or leukocytes. On the other hand, the surface of unmodified islets (control) was bound severely with platelets and leukocytes in vitro and in vivo, thereby affecting the viability and functionality of the islets. These results strongly suggest that an islet PEGylation remedy can provide an effective clinical means of attenuating IBMIR after intrahepatic islet transplantation.

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References

  1. A. M. Shapiro, J. R. Lakey, E. A. Ryan, G. S. Korbutt, E. Toth, G. L. Warnock, N. M. Kneteman, and R. V. Rajotte, N. Engl. J. Med., 343, 230 (2000).

    Article  CAS  Google Scholar 

  2. A. M. Davalli, L. Scaglia, D. H. Zangen, J. Hollister, S. Bonner-Weir, and G. C. Weir, Diabetes, 45, 1161 (1996).

    Article  CAS  Google Scholar 

  3. E. A. Ryan, J. R. Lakey, R. V. Rajotte, G. S. Korbutt, T. Kin, S. Imes, A. Rabinovitch, J. F. Elliott, D. Bigam, N. M. Kneteman, G. L. Warnock, I. Larsen, and A. M. Shapiro, Diabetes, 50, 710 (2001).

    Article  CAS  Google Scholar 

  4. W. Bennet, B. Sundberg, C. G. Groth, M. D. Brendel, D. Brandhorst, H. Brandhorst, R. G. Bretzel, G. Elgue, R. Larsson, B. Nilsson, and O. Korsgren, Diabetes, 48, 1907 (1999).

    Article  CAS  Google Scholar 

  5. L. Moberg, H. Johansson, A. Lukinius, C. Berne, A. Foss, R. Kallen, O. Ostraat, K. Salmela, A. Tibell, G. Tufveson, G. Elgue, K. Nilsson Ekdahl, O. Korsgren, and B. Nilsson, Lancet, 360, 2039 (2002).

    Article  CAS  Google Scholar 

  6. L. Ozmen, K. N. Ekdahl, G. Elgue, R. Larsson, O. Korsgren, and B. Nilsson, Diabetes, 51, 1779 (2002).

    Article  CAS  Google Scholar 

  7. U. Johansson, A. Olsson, S. Gabrielsson, B. Nilsson, and O. Korsgren, Biochem. Biophys. Res. Commun., 308, 474 (2003).

    Article  CAS  Google Scholar 

  8. M. Goto, H. Johansson, A. Maeda, G. Elgue, O. Korsgren, and B. Nilsson, Transplantation, 77, 741 (2004).

    Article  CAS  Google Scholar 

  9. H. Johansson, M. Goto, D. Dufrane, A. Siegbahn, G. Elgue, P. Gianello, O. Korsgren, and B. Nilsson, Am. J. Transplant., 6, 305 (2006).

    Article  CAS  Google Scholar 

  10. W. Cui, J. T. Wilson, J. Wen, J. Angsana, Z. Qu, C. A. Haller, and E. L. Chaikof, Am. J. Transplant., 9, 1308 (2009).

    Article  CAS  Google Scholar 

  11. L. Piemonti, B. E. Leone, R. Nano, A. Saccani, P. Monti, P. Maffi, G. Bianchi, A. Sica, G. Peri, R. Melzi, L. Aldrighetti, A. Secchi, V. Di Carlo, P. Allavena, and F. Bertuzzi, Diabetes, 51, 55 (2002).

    Article  CAS  Google Scholar 

  12. G. Waeber, T. Calandra, R. Roduit, J. A. Haefliger, C. Bonny, N. Thompson, B. Thorens, E. Temler, A. Meinhardt, M. Bacher, C. N. Metz, P. Nicod, and R. Bucala, Proc. Natl. Acad. Sci. U.S.A., 94, 4782 (1997).

    Article  CAS  Google Scholar 

  13. D. Y. Lee, S. J. Park, S. Lee, J. H. Nam, and Y. Byun, Tissue Eng., 13, 2133 (2007).

    Article  CAS  Google Scholar 

  14. D. Y. Lee, S. J. Park, J. H. Nam, and Y. Byun, J. Control. Release, 110, 290 (2006).

    Article  CAS  Google Scholar 

  15. D. Y. Lee, K. Yang, S. Lee, S. Y. Chae, K. W. Kim, M. K. Lee, D. J. Han, and Y. Byun, J. Biomed. Mater. Res., 62, 372 (2002).

    Article  CAS  Google Scholar 

  16. D. Y. Lee, J. H. Nam, and Y. Byun, Biomaterials, 28, 1957 (2007).

    Article  CAS  Google Scholar 

  17. D. Y. Lee, S. Lee, J. H. Nam, and Y. Byun, Am. J. Transplant., 6, 1820 (2006).

    Article  CAS  Google Scholar 

  18. J. H. Van Deijnen, P. T. Van Suylichem, G. H. Wolters, and R. Van Schilfgaarde, Cell Tissue Res., 277, 115 (1994).

    Article  Google Scholar 

  19. M. Kharouta, K. Miller, A. Kim, P. Wojcik, G. Kilimnik, A. Dey, D. F. Steiner, and M. Hara, Diabetes Res. Clin. Pract., 85, 252 (2009).

    Article  CAS  Google Scholar 

  20. D. Dufrane, R. M. Goebbels, I. Fdilat, Y. Guiot, and P. Gianello, Pancreas, 30, 138 (2005).

    Article  CAS  Google Scholar 

  21. A. L. Gainer, G. S. Korbutt, R. V. Rajotte, G. L. Warnock, and J. F. Elliott, Transplantation, 63, 1017 (1997).

    Article  CAS  Google Scholar 

  22. K. Cheng, D. Fraga, C. Zhang, M. Kotb, A. O. Gaber, R. V. Guntaka, and R. I. Mahato, Gene Ther., 11, 1105 (2004).

    Article  CAS  Google Scholar 

  23. A. S. Narang and R. I. Mahato, Pharmacol. Rev., 58, 194 (2006).

    Article  CAS  Google Scholar 

  24. Z. T. Bloomgarden, Diabetes Care, 27, 1506 (2004).

    Article  Google Scholar 

  25. J. Hill, Nurs. Times, 100, 40 (2004).

    Google Scholar 

  26. H. B. DuBiner, M. Mroz, A. M. Shapiro, and M. S. Dirks, Clin. Ther., 23, 1969 (2001).

    Article  CAS  Google Scholar 

  27. A. M. Shapiro, E. A. Ryan, and J. R. Lakey, Lancet, 358, S21 (2001).

    Article  Google Scholar 

  28. A. M. Shapiro, E. A. Ryan, and J. R. Lakey, Transplant. Proc., 33, 3502 (2001).

    Article  CAS  Google Scholar 

  29. A. M. Shapiro, S. A. Nanji, and J. R. Lakey, Immunol. Rev., 196, 219 (2003).

    Article  CAS  Google Scholar 

  30. C. Ricordi and T. B. Strom, Nat. Rev. Immunol., 4, 259 (2004).

    Article  CAS  Google Scholar 

  31. Y. Teramura and H. Iwata, Bioconjug. Chem., 19, 1389 (2008).

    Article  CAS  Google Scholar 

  32. S. Cabric, J. Sanchez, T. Lundgren, A. Foss, M. Felldin, R. Kallen, K. Salmela, A. Tibell, G. Tufveson, R. Larsson, O. Korsgren, and B. Nilsson, Diabetes, 56, 2008 (2007).

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Departments of Bioengineering, College of Engineering, and Institute for Bioengineering and Biopharmaceutical Research, Hanyang University, Seoul, 133-791, Korea

    Dong Yun Lee

  2. Hanyang University Institute of Aging Society, Seoul, 133-791, Korea

    Dong Yun Lee

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  1. Dong Yun Lee
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Correspondence to Dong Yun Lee.

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Lee, D.Y. Islet surface PEGylation attenuate the instant blood-mediated inflammatory reaction in intrahepatic islet transplantation. Macromol. Res. 19, 904–910 (2011). https://doi.org/10.1007/s13233-011-0904-y

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  • DOI: https://doi.org/10.1007/s13233-011-0904-y

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