Islet Surface PEGylation Attenuate the Instant Blood-Mediated Inflammatory Reaction in Intrahepatic Islet Transplantation

Dong Yun Lee

Macromolecular Research, Vol.19, No.9, 904-910, September, 2011

DOI10.1007/s13233-011-0904-y Export Citation

Islet Surface PEGylation Attenuate the Instant Blood-Mediated Inflammatory Reaction in Intrahepatic Islet Transplantation

Dong Yun Lee^{1, 2, †}

¹Departments of Bioengineering, College of Engineering, and Institute for Bioengineering and Biopharmaceutical Research, Hanyang University, Seoul, 133-791, Korea
²Hanyang University Institute of Aging Society, Seoul, 133-791, Korea

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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.

Keywords:pancreatic islet;PEGylation;intrahepatic transplantation;instant blood mediated inflammatory reaction (IBMIR);platelet.

[References]

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[2] Davalli AM, Scaglia L, Zangen DH, Hollister J, Bonner-Weir S, Weir GC, Diabetes, 45, 1161 (1996)

[3] Ryan EA, Lakey JR, Rajotte RV, Korbutt GS, Kin T, Imes S, Rabinovitch A, Elliott JF, Bigam D, Kneteman NM, Warnock GL, Larsen I, Shapiro AM, Diabetes, 50, 710 (2001)

[4] Bennet W, Sundberg B, Groth CG, Brendel MD, Brandhorst D, Brandhorst H, Bretzel RG, Elgue G, Larsson R, Nilsson B, Korsgren O, Diabetes, 48, 1907 (1999)

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

[6] Ozmen L, Ekdahl KN, Elgue G, Larsson R, Korsgren O, Nilsson B, Diabetes, 51, 1779 (2002)

[7] Johansson U, Olsson A, Gabrielsson S, Nilsson B, Korsgren O, Biochem. Biophys. Res. Commun., 308(3), 474 (2003)

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

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

[10] Cui W, Wilson JT, Wen J, Angsana J, Qu Z, Haller CA, Chaikof EL, Am. J. Transplant., 9, 1308 (2009)

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

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

[13] Lee DY, Park SJ, Lee S, Nam JH, Byun Y, Tissue Eng., 13, 2133 (2007)

[14] Lee DY, Park SJ, Nam JH, Byun Y, J. Control. Release, 110, 290 (2006)

[15] Lee DY, Yang K, Lee S, Chae SY, Kim KW, Lee MK, Han DJ, Byun Y, J. Biomed. Mater. Res., 62, 372 (2002)

[16] Lee DY, Nam JH, Byun Y, Biomaterials, 28, 1957 (2007)

[17] Lee DY, Lee S, Nam JH, Byun Y, Am. J. Transplant., 6, 1820 (2006)

[18] Van Deijnen JH, Van Suylichem PT, Wolters GH, Van Schilfgaarde R, Cell Tissue Res., 277, 115 (1994)

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

[20] Dufrane D, Goebbels RM, Fdilat I, Guiot Y, Gianello P, Pancreas, 30, 138 (2005)

[21] Gainer AL, Korbutt GS, Rajotte RV, Warnock GL, Elliott JF, Transplantation, 63, 1017 (1997)

[22] Cheng K, Fraga D, Zhang C, Kotb M, Gaber AO, Guntaka RV, Mahato RI, Gene Ther., 11, 1105 (2004)

[23] Narang AS, Mahato RI, Pharmacol. Rev., 58, 194 (2006)

[24] Bloomgarden ZT, Diabetes Care, 27, 1506 (2004)

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

[26] DuBiner HB, Mroz M, Shapiro AM, Dirks MS, Clin. Ther., 23, 1969 (2001)

[27] Shapiro AM, Ryan EA, Lakey JR, Lancet, 358, S21 (2001)

[28] Shapiro AM, Ryan EA, Lakey JR, Transplant. Proc., 33, 3502 (2001)

[29] Shapiro AM, Nanji SA, Lakey JR, Immunol. Rev., 196, 219 (2003)

[30] Ricordi C, Strom TB, Nat. Rev. Immunol., 4, 259 (2004)

[31] Teramura Y, Iwata H, Bioconjugate Chem., 19, 1389 (2008)

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