nach oben

Current Diabetes Reports

Erschienen in:

01.10.2013 | Transplantation (A Pileggi, Section Editor)

Anti-Inflammatory Strategies to Enhance Islet Engraftment and Survival

verfasst von: Antonio Citro, Elisa Cantarelli, Lorenzo Piemonti

Erschienen in: Current Diabetes Reports | Ausgabe 5/2013

Einloggen, um Zugang zu erhalten

Abstract

Early innate inflammatory reaction strongly affects islet engraftment and survival after intrahepatic transplantation. This early immune response is triggered by ischemia-reperfusion injury and instant blood mediated inflammatory reaction (IBMIR) occurring hours and days after islet infusion. Evidence in both mouse model and in human counterpart suggest the involvement of coagulation, complement system, and proinflammatory chemokines/cytokines. Identification and targeting of pathway(s), playing a role as “master regulator(s)” in post-transplant detrimental inflammatory events, is now mandatory to improve islet transplantation success. This review will focus on inflammatory pathway(s) differentially modulated by islet isolation and mainly associated with the early post-transplant events. Moreover, we will take into account anti-inflammatory strategies that have been tested at 2 levels: on the graft, ex vivo, during islet culture (i.e., donor) and/or on the graft site, in vivo, early after islet infusion (i.e., recipient).

•• Barton FB, Rickels MR, Alejandro R, Hering BJ, Wease S, Naziruddin B, et al. Improvement in outcomes of clinical islet transplantation: 1999–2010. Diabetes Care. 2012;35:1436–45. The most recent report of efficacy and safety outcomes in clinical islet transplantation underlining the relevance of peri-transplant anti-inflammatory strategies.

Moberg L, Johansson H, Lukinius A, Berne C, Foss A, Kallen R, et al. Production of tissue factor by pancreatic islet cells as a trigger of detrimental thrombotic reactions in clinical islet transplantation. Lancet. 2002;360:2039–45.

Nilsson B, Ekdahl KN, Korsgren O. Control of instant blood-mediated inflammatory reaction to improve islets of Langerhans engraftment. Curr Opin Organ Transplant. 2011;16:620–6.

Eriksson O, Eich T, Sundin A, Tibell A, Tufveson G, Andersson H, et al. Positron emission tomography in clinical islet transplantation. Am J Transplant. 2009;9:2816–24.

Sakata N, Hayes P, Tan A, Chan NK, Mace J, Peverini R, et al. MRI assessment of ischemic liver after intraportal islet transplantation. Transplantation. 2009;87:825–30.

Deters NA, Stokes RA, Gunton JE. Islet transplantation: factors in short-term islet survival. Arch Immunol Ther Exp (Warsz). 2011;59:421–9.CrossRef

• Shapiro AM. Strategies toward single-donor islets of Langerhans transplantation. Curr Opin Organ Transplant. 2011;16:627–31. Comprehensive analysis of pathways and strategies determining the success or failure of single-donor islet engraftment.PubMedCrossRef

Colman RW, Scott CF. When and where is factor XI activated by thrombin? Blood. 1996;87:2089.PubMed

Johansson H, Lukinius A, Moberg L, Lundgren T, Berne C, Foss A, et al. Tissue factor produced by the endocrine cells of the islets of Langerhans is associated with a negative outcome of clinical islet transplantation. Diabetes. 2005;54:1755–62.

10.

Johansson H, Goto M, Dufrane D, Siegbahn A, Elgue G, Gianello P, et al. Low molecular weight dextran sulfate: a strong candidate drug to block IBMIR in clinical islet transplantation. Am J Transplant. 2006;6:305–12.

11.

Spirig R, Gajanayake T, Korsgren O, Nilsson B, Rieben R. Low molecular weight dextran sulfate as complement inhibitor and cytoprotectant in solid organ and islet transplantation. Mol Immunol. 2008;45:4084–94.

12.

Goto M, Johansson H, Maeda A, Elgue G, Korsgren O, Nilsson B. Low molecular weight dextran sulfate prevents the instant blood-mediated inflammatory reaction induced by adult porcine islets. Transplantation. 2004;77:741–7.

13.

Cabric S, Sanchez J, Lundgren T, Foss A, Felldin M, Kallen R, et al. Islet surface heparinization prevents the instant blood-mediated inflammatory reaction in islet transplantation. Diabetes. 2007;56:2008–15.

14.

Johansson U, Elgue G, Nilsson B, Korsgren O. Composite islet-endothelial cell grafts: a novel approach to counteract innate immunity in islet transplantation. Am J Transplant. 2005;5:2632–9.

15.

Kim HI, Yu JE, Lee SY, Sul AY, Jang MS, Rashid MA, et al. The effect of composite pig islet-human endothelial cell grafts on the instant blood-mediated inflammatory reaction. Cell Transplant. 2009;18:31–7.

16.

Ozmen L, Ekdahl KN, Elgue G, Larsson R, Korsgren O, Nilsson B. Inhibition of thrombin abrogates the instant blood-mediated inflammatory reaction triggered by isolated human islets: possible application of the thrombin inhibitor melagatran in clinical islet transplantation. Diabetes. 2002;51:1779–84.

17.

Beuneu C, Vosters O, Ling Z, Pipeleers D, Pradier O, Goldman M, et al. N-Acetylcysteine derivative inhibits procoagulant activity of human islet cells. Diabetologia. 2007;50:343–7.

18.

Vosters O, Beuneu C, Goldman M, Verhasselt V. N-acetylcysteine derivative inhibits CD40-dependent proinflammatory properties of human pancreatic duct cells. Pancreas. 2008;36:363–8.

19.

Moberg L, Olsson A, Berne C, Felldin M, Foss A, Kallen R, et al. Nicotinamide inhibits tissue factor expression in isolated human pancreatic islets: implications for clinical islet transplantation. Transplantation. 2003;76:1285–8.

20.

Jung DY, Park JB, Joo SY, Joh JW, Kwon CH, Kwon GY, et al. Effect of nicotinamide on early graft failure following intraportal islet transplantation. Exp Mol Med. 2009;41:782–92.

21.

Thies JC, Teklote J, Clauer U, Tox U, Klar E, Hofmann WJ, et al. The efficacy of N-acetylcysteine as a hepatoprotective agent in liver transplantation. Transpl Int. 1998;11 Suppl 1:S390–2.

22.

Weigand MA, Plachky J, Thies JC, Spies-Martin D, Otto G, Martin E, et al. N-acetylcysteine attenuates the increase in alpha-glutathione S-transferase and circulating ICAM-1 and VCAM-1 after reperfusion in humans undergoing liver transplantation. Transplantation. 2001;72:694–8.

23.

Testa L, Andreotti F, Biondi Zoccai GG, Burzotta F, Bellocci F, Crea F. Ximelagatran/melagatran against conventional anticoagulation: a meta-analysis based on 22,639 patients. Int J Cardiol. 2007;122:117–24.

24.

• Matsuoka N, Itoh T, Watarai H, Sekine-Kondo E, Nagata N, Okamoto K, et al. High-mobility group box 1 is involved in the initial events of early loss of transplanted islets in mice. J Clin Invest. 2010;120:735–43. This study underlines the importance of HMGB1 as an ex vivo potential target for intervention.

25.

Itoh T, Takita M, Sorelle JA, Shimoda M, Sugimoto K, Chujo D, et al. Correlation of released HMGB1 levels with the degree of islet damage in mice and humans and with the outcomes of islet transplantation in mice. Cell Transplant. 2012;21(7):1371–81.

26.

Nano R, Racanicchi L, Melzi R, Mercalli A, Maffi P, Sordi V, et al. Human pancreatic islet preparations release HMGB1: (Ir)relevance for graft engraftment. Cell Transplant. 2012. doi:10.3727/096368912X657783.

27.

Itoh T, Iwahashi S, Kanak MA, Shimoda M, Takita M, Chujo D, et al. Elevation of high-mobility group box 1 after clinical autologous islet transplantation and its inverse correlation with outcomes. Cell Transplant. 2012. doi:10.3727/096368912X658980.

28.

Dumitriu IE, Baruah P, Valentinis B, Voll RE, Herrmann M, Nawroth PP, et al. Release of high mobility group box 1 by dendritic cells controls T cell activation via the receptor for advanced glycation end products. J Immunol. 2005;174:7506–15.

29.

Messmer D, Yang H, Telusma G, Knoll F, Li J, Messmer B, et al. High mobility group box protein 1: an endogenous signal for dendritic cell maturation and Th1 polarization. J Immunol. 2004;173:307–13.

30.

Penzo M, Molteni R, Suda T, Samaniego S, Raucci A, Habiel DM, et al. Inhibitor of NF-kappa B kinases alpha and beta are both essential for high mobility group box 1-mediated chemotaxis [corrected]. J Immunol. 2010;184:4497–509.

31.

Rossini A, Zacheo A, Mocini D, Totta P, Facchiano A, Castoldi R, et al. HMGB1-stimulated human primary cardiac fibroblasts exert a paracrine action on human and murine cardiac stem cells. J Mol Cell Cardiol. 2008;44:683–93.

32.

•• Negi S, Jetha A, Aikin R, Hasilo C, Sladek R, Paraskevas S. Analysis of beta-cell gene expression reveals inflammatory signaling and evidence of dedifferentiation following human islet isolation and culture. PLoS One. 2012;7:e30415. This β-cell gene expression analysis reveals the upregulation, after islet isolation and culture, of proinflammatory pathways.

33.

•• Cowley MJ, Weinberg A, Zammit NW, Walters SN, Hawthorne WJ, Loudovaris T, et al. Human islets express a marked proinflammatory molecular signature prior to transplantation. Cell Transplant. 2012;21:2063–78. This study reports the high expression by pancreatic islets of chemokines mediating neutrophil recruitment.

34.

•• Citro A, Cantarelli E, Maffi P, Nano R, Melzi R, Mercalli A, et al. CXCR1/2 inhibition enhances pancreatic islet survival after transplantation. J Clin Invest. 2012;122:3647–51. This study provides that CXCR1/2 pathway is a master regulator of islet damage and should be a target for intervention to improve the efficiency of islet transplantation.

35.

Melzi R, Mercalli A, Sordi V, Cantarelli E, Nano R, Maffi P, et al. Role of CCL2/MCP-1 in islet transplantation. Cell Transplant. 2010;19:1031–46.

36.

Lee I, Wang L, Wells AD, Ye Q, Han R, Dorf ME, et al. Blocking the monocyte chemoattractant protein-1/CCR2 chemokine pathway induces permanent survival of islet allografts through a programmed death-1 ligand-1-dependent mechanism. J Immunol. 2003;171:6929–35.

37.

Schroppel B, Zhang N, Chen P, Zang W, Chen D, Hudkins KL, et al. Differential expression of chemokines and chemokine receptors in murine islet allografts: the role of CCR2 and CCR5 signaling pathways. J Am Soc Nephrol. 2004;15:1853–61.

38.

Piemonti L, Leone BE, Nano R, Saccani A, Monti P, Maffi P, et al. Human pancreatic islets produce and secrete MCP-1/CCL2: relevance in human islet transplantation. Diabetes. 2002;51:55–65.

39.

Baumann B, Salem HH, Boehm BO. Anti-inflammatory therapy in type 1 diabetes. Curr Diab Rep. 2012;12:499–509.

40.

Rink JS, Chen X, Zhang X, Kaufman DB. Conditional and specific inhibition of NF-kappaB in mouse pancreatic beta cells prevents cytokine-induced deleterious effects and improves islet survival post-transplant. Surgery. 2012;151:330–9.

41.

Gao Q, Ma LL, Gao X, Yan W, Williams P, Yin DP. TLR4 mediates early graft failure after intraportal islet transplantation. Am J Transplant. 2010;10:1588–96.

42.

Yang H, Thomas D, Boffa DJ, Ding R, Li B, Muthukumar T, et al. Enforced c-REL deficiency prolongs survival of islet allografts1. Transplantation. 2002;74:291–8.

43.

Kutlu B, Darville MI, Cardozo AK, Eizirik DL. Molecular regulation of monocyte chemoattractant protein-1 expression in pancreatic beta-cells. Diabetes. 2003;52:348–55.

44.

Amoli MM, Mousavizadeh R, Sorouri R, Rahmani M, Larijani B. Curcumin inhibits in vitro MCP-1 release from mouse pancreatic islets. Transplant Proc. 2006;38:3035–8.

45.

Takahashi T, Matsumoto S, Matsushita M, Kamachi H, Tsuruga Y, Kasai H, et al. Donor pretreatment with DHMEQ improves islet transplantation. J Surg Res. 2010;163:e23–34.

46.

• Eldor R, Abel R, Sever D, Sadoun G, Peled A, Sionov R, et al. Inhibition of nuclear factor-κB activation in pancreatic β-cells has a protective effect on allogeneic pancreatic islet graft survival. PLoS One. 2013;8:2. The author suggests that the β-cell-specific blockade of NF-κB prolongs islet graft survival with higher graft preservation and reduced inflammation.

47.

Menger MD, Yamauchi J, Vollmar B. Revascularization and microcirculation of freely grafted islets of Langerhans. World J Surg. 2001;25:509–15.PubMedCrossRef

48.

Carlsson PO, Palm F, Mattsson G. Low revascularization of experimentally transplanted human pancreatic islets. J Clin Endocrinol Metab. 2002;87:5418–23.PubMedCrossRef

49.

Robertson RP. Pancreatic islet transplantation for diabetes: successes, limitations, and challenges for the future. Mol Genet Metab. 2001;74:200–5.PubMedCrossRef

50.

Desai NM, Goss JA, Deng S, Wolf BA, Markmann E, Palanjian M, et al. Elevated portal vein drug levels of sirolimus and tacrolimus in islet transplant recipients: local immunosuppression or islet toxicity? Transplantation. 2003;76:1623–5.

51.

Markmann JF, Rosen M, Siegelman ES, Soulen MC, Deng S, Barker CF, et al. Magnetic resonance-defined periportal steatosis following intraportal islet transplantation: a functional footprint of islet graft survival? Diabetes. 2003;52:1591–4.

52.

Lee Y, Ravazzola M, Park BH, Bashmakov YK, Orci L, Unger RH. Metabolic mechanisms of failure of intraportally transplanted pancreatic beta-cells in rats: role of lipotoxicity and prevention by leptin. Diabetes. 2007;56:2295–301.

53.

• Piemonti L, Guidotti LG, Battaglia M. Modulation of early inflammatory reactions to promote engraftment and function of transplanted pancreatic islets in autoimmune diabetes. Adv Exp Med Biol. 2010;654:725–47. This chapter evaluates the relevance of different factors involved in the early innate inflammatory reaction in vivo.PubMedCrossRef

54.

Rafael E, Ryan EA, Paty BW, Oberholzer J, Imes S, Senior P, et al. Changes in liver enzymes after clinical islet transplantation. Transplantation. 2003;76:1280–4.

55.

Barshes NR, Lee TC, Goodpastor SE, Balkrishnan R, Schock AP, Mote A, et al. Transaminitis after pancreatic islet transplantation. J Am Coll Surg. 2005;200:353–61.

56.

Titus TT, Horton PJ, Badet L, Handa A, Chang L, Agarwal A, et al. Adverse outcome of human islet-allogeneic blood interaction. Transplantation. 2003;75:1317–22.

57.

Tjernberg J, Ekdahl KN, Lambris JD, Korsgren O, Nilsson B. Acute antibody-mediated complement activation mediates lysis of pancreatic islets cells and may cause tissue loss in clinical islet transplantation. Transplantation. 2008;85:1193–9.

58.

Tokodai K, Goto M, Inagaki A, Nakanishi W, Ogawa N, Satoh K, et al. Attenuation of cross-talk between the complement and coagulation cascades by C5a blockade improves early outcomes after intraportal islet transplantation. Transplantation. 2011;90:1358–65.

59.

Bennet W, Sundberg B, Lundgren T, Tibell A, Groth CG, Richards A, et al. Damage to porcine islets of Langerhans after exposure to human blood in vitro, or after intraportal transplantation to cynomologus monkeys: protective effects of sCR1 and heparin. Transplantation. 2000;69:711–9.

60.

Lundgren T, Bennet W, Tibell A, Soderlund J, Sundberg B, Song Z, et al. Soluble complement receptor 1 (TP10) preserves adult porcine islet morphology after intraportal transplantation into cynomolgus monkeys. Transplant Proc. 2001;33:725.

61.

Tokodai K, Goto M, Inagaki A, Nakanishi W, Okada N, Okada H, et al. C5a-inhibitory peptide combined with gabexate mesilate prevents the instant blood-mediated inflammatory reaction in a rat model of islet transplantation. Transplant Proc. 2010;42:2102–3.

62.

Rittirsch D, Flierl MA, Nadeau BA, Day DE, Huber-Lang M, Mackay CR, et al. Functional roles for C5a receptors in sepsis. Nat Med. 2008;14:551–7.

63.

Zamora MR, Davis RD, Keshavjee SH, Schulman L, Levin J, Ryan U, et al. Complement inhibition attenuates human lung transplant reperfusion injury: a multicenter trial. Chest. 1999;116(1 Suppl):46S.

64.

Horstick G, Berg O, Heimann A, Gotze O, Loos M, Hafner G, et al. Application of C1-esterase inhibitor during reperfusion of ischemic myocardium: dose-related beneficial vs detrimental effects. Circulation. 2001;104:3125–31.

65.

Berman DM, Cabrera O, Kenyon NM, Miller J, Tam SH, Khandekar VS, et al. Interference with tissue factor prolongs intrahepatic islet allograft survival in a nonhuman primate marginal mass model. Transplantation. 2007;84:308–15.

66.

Tseng PY, Jordan SW, Sun XL, Chaikof EL. Catalytic efficiency of a thrombomodulin-functionalized membrane-mimetic film in a flow model. Biomaterials. 2006;27:2768–75.

67.

Tseng PY, Rele SS, Sun XL, Chaikof EL. Membrane-mimetic films containing thrombomodulin and heparin inhibit tissue factor-induced thrombin generation in a flow model. Biomaterials. 2006;27:2637–50.

68.

Cui W, Wilson JT, Wen J, Angsana J, Qu Z, Haller CA. Thrombomodulin improves early outcomes after intraportal islet transplantation. Am J Transplant. 2009;9:1308–16.

69.

Moberg L, Korsgren O, Nilsson B. Neutrophilic granulocytes are the predominant cell type infiltrating pancreatic islets in contact with ABO-compatible blood. Clin Exp Immunol. 2005;142:125–31.PubMedCrossRef

70.

Melzi R, Sanvito F, Mercalli A, Andralojc K, Bonifacio E, Piemonti L. Intrahepatic islet transplant in the mouse: functional and morphological characterization. Cell Transplant. 2008;17:1361–70.

71.

Bertini R, Allegretti M, Bizzarri C, Moriconi A, Locati M, Zampella G, et al. Noncompetitive allosteric inhibitors of the inflammatory chemokine receptors CXCR1 and CXCR2: prevention of reperfusion injury. Proc Natl Acad Sci U S A. 2004;101:11791–6.

72.

Casilli F, Bianchini A, Gloaguen I, Biordi L, Alesse E, Festuccia C, et al. Inhibition of interleukin-8 (CXCL8/IL-8) responses by repertaxin, a new inhibitor of the chemokine receptors CXCR1 and CXCR2. Biochem Pharmacol. 2005;69:385–94.

73.

Neri F, Puviani L, Tsivian M, Prezzi D, Pacile V, Cavallari G, et al. Protective effect of an inhibitor of interleukin-8 (meraxin) from ischemia and reperfusion injury in a rat model of kidney transplantation. Transplant Proc. 2007;39:1771–2.

74.

Villa P, Triulzi S, Cavalieri B, Di Bitondo R, Bertini R, Barbera S, et al. The interleukin-8 (IL-8/CXCL8) receptor inhibitor reparixin improves neurological deficits and reduces long-term inflammation in permanent and transient cerebral ischemia in rats. Mol Med. 2007;13:125–33.

75.

Cavalieri B, Mosca M, Ramadori P, Perrelli MG, De Simone L, Colotta F, et al. Neutrophil recruitment in the reperfused-injured rat liver was effectively attenuated by repertaxin, a novel allosteric noncompetitive inhibitor of CXCL8 receptors: a therapeutic approach for the treatment of post-ischemic hepatic syndromes. Int J Immunopathol Pharmacol. 2005;18:475–86.

76.

Alejandro R, Barton F, B. Hering B J, Wease S. 2008 update from the Collaborative Islet Transplant Registry. Transplantation. 2008;86:1783–8.

77.

Gibly RF, Graham JG, Luo X, Lowe WL Jr, Hering BJ, Shea LD. Advancing islet transplantation: from engraftment to the immune response. Diabetologia. 2011;54:2494–505.

78.

Hering BJ, Kandaswamy R, Ansite JD, Eckman PM, Nakano M, Sawada T, et al. Single-donor, marginal-dose islet transplantation in patients with type 1 diabetes. JAMA. 2005;293:830–5.

79.

Faradji RN, Tharavanij T, Messinger S, Froud T, Pileggi A, Monroy K, et al. Long-term insulin independence and improvement in insulin secretion after supplemental islet infusion under exenatide and etanercept. Transplantation. 2008;86:1658–65.

80.

Bellin MD, Kandaswamy R, Parkey J, Zhang HJ, Liu B, Ihm SH, et al. Prolonged insulin independence after islet allotransplants in recipients with type 1 diabetes. Am J Transplant. 2008;8:2463–70.

81.

Matsumoto S, Takita M, Chaussabel D, Noguchi H, Shimoda M, Sugimoto K, et al. Improving efficacy of clinical islet transplantation with iodixanol-based islet purification, thymoglobulin induction, and blockage of IL-1beta and TNF-alpha. Cell Transplant. 2011;20:1641–7.

82.

Rabinovitch A, Sumoski W, Rajotte RV, Warnock GL. Cytotoxic effects of cytokines on human pancreatic islet cells in monolayer culture. J Clin Endocrinol Metab. 1990;71:152–6.

83.

Lai Y, Chen C, Linn T. Innate immunity and heat shock response in islet transplantation. Clin Exp Immunol. 2009;157:1–8.PubMedCrossRef

84.

Bottino R, Fernandez LA, Ricordi C, Lehmann R, Tsan MF, Oliver R, et al. Transplantation of allogeneic islets of Langerhans in the rat liver: effects of macrophage depletion on graft survival and microenvironment activation. Diabetes. 1998;47:316–23.

85.

Farney AC, Xenos E, Sutherland DE, Widmer M, Stephanian E, Field MJ, et al. Inhibition of pancreatic islet beta cell function by tumor necrosis factor is blocked by a soluble tumor necrosis factor receptor. Transplant Proc. 1993;25(1 Pt 2):865–6.

86.

Ishii D, Schenk AD, Baba S, Fairchild RL. Role of TNFalpha in early chemokine production and leukocyte infiltration into heart allografts. Am J Transplant. 2009;10:59–68.

87.

Gangemi A, Salehi P, Hatipoglu B, Martellotto J, Barbaro B, Kuechle JB, et al. Islet transplantation for brittle type 1 diabetes: the UIC protocol. Am J Transplant. 2008;8:1250–61.

88.

Froud T, Ricordi C, Baidal DA, Hafiz MM, Ponte G, Cure P, et al. Islet transplantation in type 1 diabetes mellitus using cultured islets and steroid-free immunosuppression: Miami experience. Am J Transplant. 2005;5:2037–46.

89.

van Vollenhoven R, Harju A, Brannemark S, Klareskog L. Treatment with infliximab (Remicade) when etanercept (Enbrel) has failed or vice versa: data from the STURE registry showing that switching tumor necrosis factor alpha blockers can make sense. Ann Rheum Dis. 2003;62:1195–8.

90.

Billiar TR, Curran RD, Stuehr DJ, West MA, Bentz BG, Simmons RL. An L-arginine-dependent mechanism mediates Kupffer cell inhibition of hepatocyte protein synthesis in vitro. J Exp Med. 1989;169:1467–72.

91.

Nilsson B, Ekdahl KN, Korsgren O. Control of instant blood-mediated inflammatory reaction to improve islets of Langerhans engraftment. Curr Opin Organ Transplant. 2011;16:620–6.PubMedCrossRef

92.

Sandberg JO, Eizirik DL, Sandler S. IL-1 receptor antagonist inhibits recurrence of disease after syngeneic pancreatic islet transplantation to spontaneously diabetic nonobese diabetic (NOD) mice. Clin Exp Immunol. 1997;108:314–7.PubMedCrossRef

93.

Sandberg JO, Eizirik DL, Sandler S, Tracey DE, Andersson A. Treatment with an interleukin-1 receptor antagonist protein prolongs mouse islet allograft survival. Diabetes. 1993;42:1845–51.

94.

Westwell-Roper C, Dai DL, Soukhatcheva G, Potter KJ, van Rooijen N, Ehses JA, et al. IL-1 blockade attenuates islet amyloid polypeptide-induced proinflammatory cytokine release and pancreatic islet graft dysfunction. J Immunol. 2011;187:2755–65.

95.

• McCall M, Pawlick R, Kin T, Shapiro AM. Anakinra potentiates the protective effects of etanercept in transplantation of marginal mass human islets in immunodeficient mice. Am J Transplant. 2012;12:322–9. This publication evidences the possibility to peri-transplant use the association of 2 innovative anti-inflammatory strategies targeting TNFα and IL-1β to improve islet engraftment in the mouse model.

96.

• Takita M, Matsumoto S, Shimoda M, Chujo D, Itoh T, Sorelle JA, et al. Safety and tolerability of the T-cell depletion protocol coupled with anakinra and etanercept for clinical islet cell transplantation. Clin Transplant. 2012;26:E471–84. This publication evidences the possibility to peri-transplant use the association of 2 innovative anti-inflammatory strategies targeting TNFα and IL-1β to improve islet engraftment in the clinical practice.

97.

Contreras JL, Bilbao G, Smyth CA, Jiang XL, Eckhoff DE, Jenkins SM, et al. Cytoprotection of pancreatic islets before and soon after transplantation by gene transfer of the anti-apoptotic Bcl-2 gene. Transplantation. 2001;71:1015–23.

98.

Emamaullee JA, Rajotte RV, Liston P, Korneluk RG, Lakey JR, Shapiro AM, et al. XIAP overexpression in human islets prevents early posttransplant apoptosis and reduces the islet mass needed to treat diabetes. Diabetes. 2005;54:2541–8.

99.

Plesner A, Liston P, Tan R, Korneluk RG, Verchere CB. The X-linked inhibitor of apoptosis protein enhances survival of murine islet allografts. Diabetes. 2005;54:2533–40.

100.

Qin J, Jiao Y, Chen X, Zhou S, Liang C, Zhong C. Overexpression of suppressor of cytokine signaling 1 in islet grafts results in anti-apoptotic effects and prolongs graft survival. Life Sci. 2009;84:810–6.

101.

Grey ST, Longo C, Shukri T, Patel VI, Csizmadia E, Daniel S, et al. Genetic engineering of a suboptimal islet graft with A20 preserves beta cell mass and function. J Immunol. 2003;170:6250–6.

102.

Montolio M, Téllez N, Biarnés M, Soler J, Montanya E. Short-term culture with the caspase inhibitor z-VAD.fmk reduces beta cell apoptosis in transplanted islets and improves the metabolic outcome of the graft. Cell Transplant. 2005;14:59–65.

103.

Emamaullee JA, Stanton L, Schur C, Shapiro AM. Caspase inhibitor therapy enhances marginal mass islet graft survival and preserves long-term function in islet transplantation. Diabetes. 2007;56:1289–98.

104.

Emamaullee JA, Davis J, Pawlick R, Toso C, Merani S, Cai SX, et al. The caspase selective inhibitor EP1013 augments human islet graft function and longevity in marginal mass islet transplantation in mice. Diabetes. 2008;57:1556–66.

105.

Baskin-Bey ES, Washburn K, Feng S, Oltersdorf T, Shapiro D, Huyghe M, et al. Clinical trial of the pan-caspase inhibitor, IDN-6556, in human liver preservation injury. Am J Transplant. 2007;7:218–25.

106.

•• McCall M, Toso C, Emamaullee J, Pawlick R, Edgar R, Davis J, et al. The caspase inhibitor IDN-6556 (PF3491390) improves marginal mass engraftment after islet transplantation in mice. Surgery. 2011;150:48–55. This relevant publication evaluates for the first time the use of the caspase inhibitor IDN-6556 as an anti-inflammatory strategy in a pre-clinical model of islet transplantation.

107.

McCall MD, Maciver AM, Kin T, Emamaullee J, Pawlick R, Edgar R, et al. Caspase inhibitor IDN6556 facilitates marginal mass islet engraftment in a porcine islet autotransplant model. Transplantation. 2012;94:30–5.

108.

Cechin SR, Pérez-Álvarez I, Fenjves E, Molano RD, Pileggi A, Berggren PO, et al. Anti-inflammatory properties of exenatide in human pancreatic islets. Cell Transplant. 2012;21:633–48.

109.

King A, Lock J, Xu G, Bonner-Weir S, Weir GC. Islet transplantation outcomes in mice are better with fresh islets and exendin-4 treatment. Diabetologia. 2005;48:2074–9.

110.

Toyoda K, Okitsu T, Yamane S, Uonaga T, Liu X, Harada N, et al. GLP-1 receptor signaling protects pancreatic beta cells in intraportal islet transplant by inhibiting apoptosis. Biochem Biophys Res Commun. 2008;367:793–8.

111.

Padmasekar M, Lingwal N, Samikannu B, Chen C, Sauer H, Linn T. Exendin-4 protects hypoxic islets from oxidative stress and improves islet transplantation outcome. Endocrinology. 2013;154:1424–33

112.

Merani S, Truong W, Emamaullee JA, Toso C, Knudsen LB, Shapiro AM. Liraglutide, a long-acting human glucagon-like peptide 1 analog, improves glucose homeostasis in marginal mass islet transplantation in mice. Endocrinology. 2008;149:4322–8.

113.

Emamaullee JA, Merani S, Toso C, Kin T, Al-Saif F, Truong W, et al. Porcine marginal mass islet autografts resist metabolic failure over time and are enhanced by early treatment with liraglutide. Endocrinology. 2009;150:2145–52.

114.

Mestas J, Hughes CC. Of mice and not men: differences between mouse and human immunology. J Immunol. 2004;172:2731–8.PubMed

Titel: Anti-Inflammatory Strategies to Enhance Islet Engraftment and Survival
verfasst von: Antonio Citro
Elisa Cantarelli
Lorenzo Piemonti
Publikationsdatum: 01.10.2013
Verlag: Springer US
Erschienen in: Current Diabetes Reports / Ausgabe 5/2013
Print ISSN: 1534-4827
Elektronische ISSN: 1539-0829
DOI: https://doi.org/10.1007/s11892-013-0401-0

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Neu im Fachgebiet Innere Medizin

Reizdarmsyndrom: Diäten wirksamer als Medikamente

29.04.2024 Reizdarmsyndrom Nachrichten

Bei Reizdarmsyndrom scheinen Diäten, wie etwa die FODMAP-arme oder die kohlenhydratreduzierte Ernährung, effektiver als eine medikamentöse Therapie zu sein. Das hat eine Studie aus Schweden ergeben, die die drei Therapieoptionen im direkten Vergleich analysierte.

Notfall-TEP der Hüfte ist auch bei 90-Jährigen machbar

26.04.2024 Hüft-TEP Nachrichten

Ob bei einer Notfalloperation nach Schenkelhalsfraktur eine Hemiarthroplastik oder eine totale Endoprothese (TEP) eingebaut wird, sollte nicht allein vom Alter der Patientinnen und Patienten abhängen. Auch über 90-Jährige können von der TEP profitieren.

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

25.04.2024 Hypotonie Nachrichten

Wenn unter einer medikamentösen Hochdrucktherapie der diastolische Blutdruck in den Keller geht, steigt das Risiko für schwere kardiovaskuläre Ereignisse: Darauf deutet eine Sekundäranalyse der SPRINT-Studie hin.

Bei schweren Reaktionen auf Insektenstiche empfiehlt sich eine spezifische Immuntherapie

25.04.2024 Allergien und Intoleranzreaktionen Nachrichten

Insektenstiche sind bei Erwachsenen die häufigsten Auslöser einer Anaphylaxie. Einen wirksamen Schutz vor schweren anaphylaktischen Reaktionen bietet die allergenspezifische Immuntherapie. Jedoch kommt sie noch viel zu selten zum Einsatz.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 5/2013

Screening, Prevention, and Ambitious Management of Diabetic Macular Edema in Patients with Type 1 Diabetes

Making β Cells from Adult Cells Within the Pancreas

Novel Diabetes Autoantibodies and Prediction of Type 1 Diabetes

Continuous Glucose Monitoring: Current Use and Future Directions

Human Intestinal Microbiota and Type 1 Diabetes