Layer-by-layer building up of heparin and glycol chitosan for rat pancreatic islet xenotransplantation to mouse

Sung Woo Hong; Jee-Heon Jeong; Dong Yun Lee; Youngro Byun

Macromolecular Research, Vol.21, No.8, 911-915, August, 2013

DOI10.1007/s13233-013-1103-9 Export Citation

Layer-by-layer building up of heparin and glycol chitosan for rat pancreatic islet xenotransplantation to mouse

Sung Woo Hong¹, Jee-Heon Jeong², Dong Yun Lee³, and Youngro Byun^{1, 2, †}

¹Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, 151-742, Korea
²Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul, 151-742, Korea
³Department of Bioengineering, College of Engineering, and Institute for Bioengineering and Biopharmaceutical Research, Hanyang University, Seoul, 133-791, Korea

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Immunoprotective strategies are being developed to improve the graft survival rate of islets. Heparin, which has been widely used due to its anti-coagulant and anti-inflammatory effects, holds great promise for use in preventing blood coagulation and related immune reactions. In this study, the layer-by-layer modification of islets using heparin and glycol chitosan as an immunoprotective remedy was examined in xenogeneic islet transplantation. The surface coverage of heparin and glycol chitosan was evaluated in vitro. The viability and functionality of layer-by-layer modified islets was evaluated using the CCK-8 assay and glucose-stimulated insulin secretion (GSIS) test, respectively. In addition, the effect of layer-by-layer on immunoprotection for transplanted islets was evaluated in a diabetic mouse model. Layer-by-layer modified islets were evenly covered with heparin and glycol chitosan. The viability of islets was not affected by the modification procedures up to the third layer modification. In addition, unmodified and layer-by-layer modified (three layers) islets transplanted into the recipients maintained a normal level of blood glucose for 9.0±0.6 and 9.0±0.5 days, respectively. However, when the recipients were administrated with FK506 and CTLA4-Ig, the median survival time of the unmodified and layer-by-layer modified islets (three layers) were 17±1.2 and 23.0±1.3 days, respectively. These results demonstrated that the combination of FK506 and CTLA4-Ig along with layer-by-layer modification using heparin and glycol chitosan showed highly improved synergic effects on the inhibition of inflammation and immune reactions.

Keywords:pancreatic islet transplantation;layer-by-layer;heparin;glycol chitosan;Tacrolimus (FK506);CTLA4-Ig

[References]

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Molinari M, Al-Saif F, Ryan EA, Lakey JR, Senior PA, Paty BW, Bigam DL, Kneteman NM, Shapiro AM, Am. J. Transplant., 5, 2799 (2005)
Larsen JL, Bennett RG, Burkman T, Ramirez AL, Yamamoto S, Gulizia J, Radio S, Hamel FG, Transplantation, 82, 466 (2006)
Nanji SA, Shapiro AM, BioDrugs, 18, 315 (2004)
Sorenby AK, Wu GS, Zhu S, Wernerson AM, Sumitran-Holgersson S, Tibell AB, Transplantation, 82, 393 (2006)
Gray DW, Transplantation, 82, 310 (2006)
Prochorov AV, Roudenok VV, Goranov VA, Transplant. Proc., 37, 4446 (2005)
Jung YS, Jeong JH, Yook S, Im BH, Seo J, Hong SW, Park JB, Yang VC, Lee DY, Byun Y, Biomaterials, 33, 295 (2012)
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)
Wilson JT, Cui W, Chaikof EL, Nano Lett., 8, 1940 (2008)
Totani T, Teramura Y, Iwata H, Biomaterials, 29, 2878 (2008)
Teramura Y, Kaneda Y, Iwata H, Biomaterials, 28, 4818 (2007)
Takemoto N, Teramura Y, Iwata H, Bioconjugate Chem., 22, 673 (2011)
Jeong JH, Hong SW, Hong S, Yook S, Jung Y, Park JB, Khue CD, Im BH, Seo J, Lee H, Ahn CH, Lee DY, Byun Y, Biomaterials, 32, 7961 (2011)
Lee DY, Lee S, Nam JH, Byun Y, Am. J. Transplant., 6, 1820 (2006)
Mandrup-Poulsen T, Bendtzen K, Nerup J, Dinarello CA, Svenson M, Nielsen JH, Diabetologia, 29, 63 (1986)
Pukel C, Baquerizo H, Rabinovitch A, Diabetes, 37, 133 (1988)
Gibly RF, Graham JG, Luo X, Lowe WL, Hering BJ, Shea LD, Diabetologia, 54, 2494 (2011)

[Referenced By]

[1] Shapiro AM, Ricordi C, Hering BJ, Auchincloss H, Lindblad R, Robertson RP, Secchi A, Brendel MD, Berney T, Brennan DC, Cagliero E, Alejandro R, Ryan EA, DiMercurio B, Morel P, Polonsky KS, Reems JA, Bretzel RG, Bertuzzi F, Froud T, Kandaswamy R, Sutherlan, N. Engl. J. Med., 355, 1318 (2006)

[2] Merani S, Shapiro AM, Clin. Sci., 110, 611 (2006)

[3] Molinari M, Al-Saif F, Ryan EA, Lakey JR, Senior PA, Paty BW, Bigam DL, Kneteman NM, Shapiro AM, Am. J. Transplant., 5, 2799 (2005)

[4] Larsen JL, Bennett RG, Burkman T, Ramirez AL, Yamamoto S, Gulizia J, Radio S, Hamel FG, Transplantation, 82, 466 (2006)

[5] Nanji SA, Shapiro AM, BioDrugs, 18, 315 (2004)

[6] Sorenby AK, Wu GS, Zhu S, Wernerson AM, Sumitran-Holgersson S, Tibell AB, Transplantation, 82, 393 (2006)

[7] Gray DW, Transplantation, 82, 310 (2006)

[8] Prochorov AV, Roudenok VV, Goranov VA, Transplant. Proc., 37, 4446 (2005)

[9] Jung YS, Jeong JH, Yook S, Im BH, Seo J, Hong SW, Park JB, Yang VC, Lee DY, Byun Y, Biomaterials, 33, 295 (2012)

[10] 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)

[11] Wilson JT, Cui W, Chaikof EL, Nano Lett., 8, 1940 (2008)

[12] Totani T, Teramura Y, Iwata H, Biomaterials, 29, 2878 (2008)

[13] Teramura Y, Kaneda Y, Iwata H, Biomaterials, 28, 4818 (2007)

[14] Takemoto N, Teramura Y, Iwata H, Bioconjugate Chem., 22, 673 (2011)

[15] Jeong JH, Hong SW, Hong S, Yook S, Jung Y, Park JB, Khue CD, Im BH, Seo J, Lee H, Ahn CH, Lee DY, Byun Y, Biomaterials, 32, 7961 (2011)

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

[17] Mandrup-Poulsen T, Bendtzen K, Nerup J, Dinarello CA, Svenson M, Nielsen JH, Diabetologia, 29, 63 (1986)

[18] Pukel C, Baquerizo H, Rabinovitch A, Diabetes, 37, 133 (1988)

[19] Gibly RF, Graham JG, Luo X, Lowe WL, Hering BJ, Shea LD, Diabetologia, 54, 2494 (2011)