Synergism of highly transducible adenovirus encoding heme oxygenase 1 gene and low-dose immunosuppressants for successful outcomes of xenotransplanted pancreatic islet

Min Jun Kim; Zahid Alam; Eonju Oh; Yong Hwa Hwang; Yong-kyu Lee; Chae-Ok Yun; Dong Yun Lee

Journal of Industrial and Engineering Chemistry, Vol.47, 202-213, March, 2017

DOI10.1016/j.jiec.2016.11.033 Export Citation

Synergism of highly transducible adenovirus encoding heme oxygenase 1 gene and low-dose immunosuppressants for successful outcomes of xenotransplanted pancreatic islet

Min Jun Kim^{1, 2}, Zahid Alam³, Eonju Oh^{1, 2}, Yong Hwa Hwang^{1, 2}, Yong-kyu Lee^{4, †}, Chae-Ok Yun^{1, 2, †}, and Dong Yun Lee^{1, 2, †}

¹Department of Bioengineering, College of Engineering, Hanyang University, Seoul 04763, Republic of Korea
²Department of Bioengineering, BK21 PLUS Future Biopharmaceutical Human Resources Training and Research Team, Hanyang University, Seoul 04763, Republic of Korea
³Designed Animal & Transplantation Research Institute, Institute of Green Bio Science & Technology, Seoul National University, Gangwon-do 25354, Republic of Korea
⁴Department of Chemical and Biological Engineering, Korea National University of Transportation, Chungju 380-702, Republic of Korea

E-mail:, ,

Pancreatic islet transplantation is a promising strategy for diabetic patients. Unfortunately, host’s immune cells rapidly reject transplanted islets. Cytoprotective gene therapy has been tried to protect them. However, the transduce yield of ex vivo gene delivery into islets is very rare due to the anatomical structure of them. Therefore, we newly designed an Arg-Gly-Asp (RGD) peptide-incorporated adenovirus vector expressing cytoprotective heme oxygenase-1 (HO1) gene (RGD-Adv-HO1) for effective gene therapy to islets via RGD.integrin interaction between adenovirus and islet. After exposure to islets, the transduced RGD-Adv-HO1 did not affect the viability and insulin secretion of islets with higher transduction efficacy. Moreover, HO1 showed cytoprotective effect from the presence of paraquat-induced reactive oxygen species (ROS). When the transduced islets were xenotransplanted into streptozotocin-induced diabetic Balb/c mice, their survival time in vivo was significantly prolonged with curing blood glucose level, which was attributed to the stable expression of HO1. Additionally, we found that RGD-Adv-HO1 showed a good synergistic effect in xenotransplanted islets when accompanied with low dose of immunosuppressants tacrolimus and anti-CD154 monoclonal antibody. Collectively, this new combinatorial remedy of RGD-Adv-HO1 transduction with low dose of immunosuppressive agents could be an effective therapy for successful outcome of islet transplantation.

Keywords:Pancreatic islet;RGD-incorporated adenovirus;Heme oxygenase-1;Low-dose immunosuppressant;Diabetes

[References]

Bottino R, Fernandez LA, Ricordi C, Lehmann R, Tsan MF, Oliver R, Inverardi L, Diabetes, 47, 316 (1998)
Corbett JA, Sweetland MA, Wang JL, Lancaster JR, McDaniel ML, Proc. Natl. Acad. Sci. U. S. A., 90, 1731 (1993)
Rabinovitch A, Suarez-Pinzon WL, Strynadka K, Lakey JR, Rajotte RV, J. Clin.Endocrinol. Metab., 81, 3197 (1996)
Shapiro AMJ, Ricordi C, Hering BJ, Auchincloss H, Lindblad R, Robertson P, 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)
Shapiro AM, Lakey JR, Ryan EA, Korbutt GS, Toth E, Warnock GL, Kneteman NM, Rajotte RV, N. Engl. J. Med., 343, 230 (2000)
Ayres RCS, Dousset B, Wixon S, Buckels JAC, Mcmaster P, Mayer AD, Lancet, 343, 862 (1994)
Berthoux F, Nephrol. Dial. Transpl., 17, 2 (2002)
Pascual M, Theruvath T, Kawai T, Tolkoff-Rubin N, Cosimi AB, N. Engl. J. Med., 346, 580 (2002)
Radu RG, Fujimoto S, Mukai E, Takehiro M, Shimono D, Nabe K, Shimodahira M, Kominato R, Aramaki Y, Nishi Y, Funakoshi S, Yamada Y, Seino Y, Am. J. Physiol. Endocrinol. Metab., 288, E365 (2005)
Durante W, Kroll MH, Christodoulides N, Peyton KJ, Schafer AI, Circ. Res., 80, 557 (1997)
Foresti R, Clark JE, Green CJ, Motterlini R, J. Biol. Chem., 272, 18411 (1997)
Rizzardini M, Terao M, Falciani F, Cantoni L, Biochem. J., 290(Pt 2), 343 (1993)
Pileggi A, Molano RD, Berney T, Cattan P, Vizzardelli C, Oliver R, Fraker C, Ricordi C, Pastori RL, Bach FH, Inverardi L, Diabetes, 50, 1983 (2001)
Maines MD, Faseb J., 2, 2557 (1988)
Gunther L, Berberat PO, Haga M, Brouard S, Smith RN, Soares MP, Bach FH, Tobiasch E, Diabetes, 51, 994 (2002)
Balla G, Jacob HS, Balla J, Rosenberg M, Nath K, Apple F, Eaton JW, Vercellotti GM, J. Biol. Chem., 267, 18148 (1992)
Bergelson JM, Cunningham JA, Droguett G, Kurtjones EA, Krithivas A, Hong JS, Horwitz MS, Crowell RL, Finberg RW, Science, 275(5304), 1320 (1997)
Bergelson JM, Krithivas A, Celi L, Droguett G, Horwitz MS, Wickham T, Crowell RL, Finberg RW, J. Virol., 72, 415 (1998)
Tomko RP, Xu R, Philipson L, Proc. Natl. Acad. Sci. U. S. A., 94, 3352 (1997)
Kay MA, Glorioso JC, Naldini L, Nat. Med., 7, 33 (2001)
Contreras JL, Wu H, Smyth CA, Eckstein CP, Young CJ, Seki T, Bilbao G, Curiel DT, Eckhoff DE, Transplantation, 76, 252 (2003)
Yotnda P, Onishi H, Heslop HE, Shayakhmetov D, Lieber A, Brenner M, Davis A, Gene Ther., 8, 930 (2001)
Yotnda P, Zompeta C, Heslop HE, Andreeff M, Brenner MK, Marini F, Hum. Gene Ther., 15, 1229 (2004)
Wu H, Yoon AR, Li F, Yun CO, Mahato RI, J. Gene Med., 13, 658 (2011)
Yoo JY, Kim JH, Kwon YG, Kim EC, Kim NK, Choi HJ, Yun CO, Mol. Ther.: J. Am. Soc. Gene Ther., 15, 295 (2007)
Nemerow GR, Stewart PL, Microbiol. Mol. Biol. Rev.: MMBR, 63, 725 (1999)
Jung HS, Lim KS, Kim MJ, Hwang YH, Yoo C, Lee YK, Kim YH, Lee DY, J. Control. Release, 172, 1092 (2013)
Sutton R, Peters M, McShane P, Gray DW, Morris PJ, Transplantation, 42, 689 (1986)
Bilbao G, Contreras JL, Dmitriev I, Smyth CA, Jenkins S, Eckhoff D, Thomas F, Thomas J, Curiel DT, Am. J. Transplant., 2, 237 (2002)
Tropea F, Troiano L, Monti D, Lovato E, Malorni W, Rainaldi G, Mattana P, Viscomi G, Ingletti MC, Portolani M, et al., Exp. Cell Res., 218, 63 (1995)
Weber M, Deng S, Kucher T, Shaked A, Ketchum RJ, Brayman KL, J. Surg. Res., 69, 23 (1997)
Cirulli V, Beattie GM, Klier G, Ellisman M, Ricordi C, Quaranta V, Frasier F, Ishii JK, Hayek A, Salomon DR, J. Cell Biol., 150, 1445 (2000)
Barbu AR, Akusjarvi G, Welsh N, Endocrinology, 146, 2406 (2005)
Bain JR, Schisler JC, Takeuchi K, Newgard CB, Becker TC, Diabetes, 53, 2190 (2004)
Stocker R, Yamamoto Y, Mcdonagh AF, Glazer AN, Ames BN, Science, 235, 1043 (1987)
Motterlini R, Foresti R, Intaglietta M, Winslow RM, Am. J. Physiol., 270, H107 (1996)
Otterbein LE, Kolls JK, Mantell LL, Cook JL, Alam J, Choi AM, J. Clin. Investig., 103, 1047 (1999)
Li Y, Li G, Dong W, Chen J, Lu D, Tan J, Pancreas, 33, 280 (2006)
Graham ML, Bellin MD, Papas KK, Hering BJ, Schuurman HJ, Xenotrans-plantation, 18, 328 (2011)
Nishimura R, Nishioka S, Fujisawa I, Shiku H, Shimada M, Sekiguchi S, Fujimori K, Ushiyama A, Matsue T, Ohuchi N, Satomi S, Goto M, PloS One, 8, e56799 (2013)
Kawai T, Andrews D, Colvin RB, Sachs DH, Cosimi B, Nat. Med., 6, 114 (2000)
Robles-Carrillo L, Meyer T, Hatfield M, Desai H, Davila M, Langer F, Amaya M, Garber E, Francis JL, Hsu YM, Amirkhosravi A, J. Immunol., 185, 1577 (2010)
Yoshimura N, Matsui S, Hamashima T, Oka T, Transplantation, 47, 351 (1989)
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)
Xia ZJ, Chang JH, Zhang L, Jiang WQ, Guan ZZ, Liu JW, Zhang Y, Hu XH, Wu GH, Wang HQ, Chen ZC, Chen JC, Zhou QH, Lu JW, Fan QX, Huang JJ, Zheng X, Chin. J. Cancer, 23, 1666 (2004)
Rodriguez-Garcia A, Gimenez-Alejandre M, Rojas JJ, Moreno R, Bazan-Peregrino M, Cascallo M, Alemany R, Clin. Cancer Res., 21, 1406 (2015)
Tsikkinis A, Cihoric N, Giannarini G, Hinz S, Briganti A, Wust P, Ost P, Ploussard G, Massard C, Surcel CI, Sooriakumaran P, Isbarn H, De Visschere PJL, Futterer JJ, van der Bergh RCN, Dal Pra A, Aebersold DM, Budach V, Ghadjar P, Eur. Urol. Focus., 1, 173 (2015)
Duerksenhughes P, Wold WSM, Gooding LR, J. Immunol. Methods, 143, 4193 (1989)
Gooding LR, Ranheim TS, Tollefson AE, Aquino L, Duerksenhughes P, Horton TM, Wold WSM, J. Virol., 65, 4114 (1991)
Muruve DA, Manfro RC, Strom TB, Libermann TA, Transplantation, 64, 542 (1997)
Sarrazy V, Koehler A, Chow ML, Zimina E, Li CX, Kato H, Caldarone CA, Hinz B, Cardiovasc. Res., 102, 407 (2014)

[Referenced By]

[1] Bottino R, Fernandez LA, Ricordi C, Lehmann R, Tsan MF, Oliver R, Inverardi L, Diabetes, 47, 316 (1998)

[2] Corbett JA, Sweetland MA, Wang JL, Lancaster JR, McDaniel ML, Proc. Natl. Acad. Sci. U. S. A., 90, 1731 (1993)

[3] Rabinovitch A, Suarez-Pinzon WL, Strynadka K, Lakey JR, Rajotte RV, J. Clin.Endocrinol. Metab., 81, 3197 (1996)

[4] Shapiro AMJ, Ricordi C, Hering BJ, Auchincloss H, Lindblad R, Robertson P, 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)

[5] Shapiro AM, Lakey JR, Ryan EA, Korbutt GS, Toth E, Warnock GL, Kneteman NM, Rajotte RV, N. Engl. J. Med., 343, 230 (2000)

[6] Ayres RCS, Dousset B, Wixon S, Buckels JAC, Mcmaster P, Mayer AD, Lancet, 343, 862 (1994)

[7] Berthoux F, Nephrol. Dial. Transpl., 17, 2 (2002)

[8] Pascual M, Theruvath T, Kawai T, Tolkoff-Rubin N, Cosimi AB, N. Engl. J. Med., 346, 580 (2002)

[9] Radu RG, Fujimoto S, Mukai E, Takehiro M, Shimono D, Nabe K, Shimodahira M, Kominato R, Aramaki Y, Nishi Y, Funakoshi S, Yamada Y, Seino Y, Am. J. Physiol. Endocrinol. Metab., 288, E365 (2005)

[10] Durante W, Kroll MH, Christodoulides N, Peyton KJ, Schafer AI, Circ. Res., 80, 557 (1997)

[11] Foresti R, Clark JE, Green CJ, Motterlini R, J. Biol. Chem., 272, 18411 (1997)

[12] Rizzardini M, Terao M, Falciani F, Cantoni L, Biochem. J., 290(Pt 2), 343 (1993)

[13] Pileggi A, Molano RD, Berney T, Cattan P, Vizzardelli C, Oliver R, Fraker C, Ricordi C, Pastori RL, Bach FH, Inverardi L, Diabetes, 50, 1983 (2001)

[14] Maines MD, Faseb J., 2, 2557 (1988)

[15] Gunther L, Berberat PO, Haga M, Brouard S, Smith RN, Soares MP, Bach FH, Tobiasch E, Diabetes, 51, 994 (2002)

[16] Balla G, Jacob HS, Balla J, Rosenberg M, Nath K, Apple F, Eaton JW, Vercellotti GM, J. Biol. Chem., 267, 18148 (1992)

[17] Bergelson JM, Cunningham JA, Droguett G, Kurtjones EA, Krithivas A, Hong JS, Horwitz MS, Crowell RL, Finberg RW, Science, 275(5304), 1320 (1997)

[18] Bergelson JM, Krithivas A, Celi L, Droguett G, Horwitz MS, Wickham T, Crowell RL, Finberg RW, J. Virol., 72, 415 (1998)

[19] Tomko RP, Xu R, Philipson L, Proc. Natl. Acad. Sci. U. S. A., 94, 3352 (1997)

[20] Kay MA, Glorioso JC, Naldini L, Nat. Med., 7, 33 (2001)

[21] Contreras JL, Wu H, Smyth CA, Eckstein CP, Young CJ, Seki T, Bilbao G, Curiel DT, Eckhoff DE, Transplantation, 76, 252 (2003)

[22] Yotnda P, Onishi H, Heslop HE, Shayakhmetov D, Lieber A, Brenner M, Davis A, Gene Ther., 8, 930 (2001)

[23] Yotnda P, Zompeta C, Heslop HE, Andreeff M, Brenner MK, Marini F, Hum. Gene Ther., 15, 1229 (2004)

[24] Wu H, Yoon AR, Li F, Yun CO, Mahato RI, J. Gene Med., 13, 658 (2011)

[25] Yoo JY, Kim JH, Kwon YG, Kim EC, Kim NK, Choi HJ, Yun CO, Mol. Ther.: J. Am. Soc. Gene Ther., 15, 295 (2007)

[26] Nemerow GR, Stewart PL, Microbiol. Mol. Biol. Rev.: MMBR, 63, 725 (1999)

[27] Jung HS, Lim KS, Kim MJ, Hwang YH, Yoo C, Lee YK, Kim YH, Lee DY, J. Control. Release, 172, 1092 (2013)

[28] Sutton R, Peters M, McShane P, Gray DW, Morris PJ, Transplantation, 42, 689 (1986)

[29] Bilbao G, Contreras JL, Dmitriev I, Smyth CA, Jenkins S, Eckhoff D, Thomas F, Thomas J, Curiel DT, Am. J. Transplant., 2, 237 (2002)

[30] Tropea F, Troiano L, Monti D, Lovato E, Malorni W, Rainaldi G, Mattana P, Viscomi G, Ingletti MC, Portolani M, et al., Exp. Cell Res., 218, 63 (1995)

[31] Weber M, Deng S, Kucher T, Shaked A, Ketchum RJ, Brayman KL, J. Surg. Res., 69, 23 (1997)

[32] Cirulli V, Beattie GM, Klier G, Ellisman M, Ricordi C, Quaranta V, Frasier F, Ishii JK, Hayek A, Salomon DR, J. Cell Biol., 150, 1445 (2000)

[33] Barbu AR, Akusjarvi G, Welsh N, Endocrinology, 146, 2406 (2005)

[34] Bain JR, Schisler JC, Takeuchi K, Newgard CB, Becker TC, Diabetes, 53, 2190 (2004)

[35] Stocker R, Yamamoto Y, Mcdonagh AF, Glazer AN, Ames BN, Science, 235, 1043 (1987)

[36] Motterlini R, Foresti R, Intaglietta M, Winslow RM, Am. J. Physiol., 270, H107 (1996)

[37] Otterbein LE, Kolls JK, Mantell LL, Cook JL, Alam J, Choi AM, J. Clin. Investig., 103, 1047 (1999)

[38] Li Y, Li G, Dong W, Chen J, Lu D, Tan J, Pancreas, 33, 280 (2006)

[39] Graham ML, Bellin MD, Papas KK, Hering BJ, Schuurman HJ, Xenotrans-plantation, 18, 328 (2011)

[40] Nishimura R, Nishioka S, Fujisawa I, Shiku H, Shimada M, Sekiguchi S, Fujimori K, Ushiyama A, Matsue T, Ohuchi N, Satomi S, Goto M, PloS One, 8, e56799 (2013)

[41] Kawai T, Andrews D, Colvin RB, Sachs DH, Cosimi B, Nat. Med., 6, 114 (2000)

[42] Robles-Carrillo L, Meyer T, Hatfield M, Desai H, Davila M, Langer F, Amaya M, Garber E, Francis JL, Hsu YM, Amirkhosravi A, J. Immunol., 185, 1577 (2010)

[43] Yoshimura N, Matsui S, Hamashima T, Oka T, Transplantation, 47, 351 (1989)

[44] 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)

[45] Xia ZJ, Chang JH, Zhang L, Jiang WQ, Guan ZZ, Liu JW, Zhang Y, Hu XH, Wu GH, Wang HQ, Chen ZC, Chen JC, Zhou QH, Lu JW, Fan QX, Huang JJ, Zheng X, Chin. J. Cancer, 23, 1666 (2004)

[46] Rodriguez-Garcia A, Gimenez-Alejandre M, Rojas JJ, Moreno R, Bazan-Peregrino M, Cascallo M, Alemany R, Clin. Cancer Res., 21, 1406 (2015)

[47] Tsikkinis A, Cihoric N, Giannarini G, Hinz S, Briganti A, Wust P, Ost P, Ploussard G, Massard C, Surcel CI, Sooriakumaran P, Isbarn H, De Visschere PJL, Futterer JJ, van der Bergh RCN, Dal Pra A, Aebersold DM, Budach V, Ghadjar P, Eur. Urol. Focus., 1, 173 (2015)

[48] Duerksenhughes P, Wold WSM, Gooding LR, J. Immunol. Methods, 143, 4193 (1989)

[49] Gooding LR, Ranheim TS, Tollefson AE, Aquino L, Duerksenhughes P, Horton TM, Wold WSM, J. Virol., 65, 4114 (1991)

[50] Muruve DA, Manfro RC, Strom TB, Libermann TA, Transplantation, 64, 542 (1997)

[51] Sarrazy V, Koehler A, Chow ML, Zimina E, Li CX, Kato H, Caldarone CA, Hinz B, Cardiovasc. Res., 102, 407 (2014)