First update of the International Xenotransplantation Association consensus statement on conditions for undertaking clinical trials of porcine islet products in type 1 diabetes - Chapter 6: Patient selection for pilot clinical trials of islet xenotransplantation

Xenotransplantation

Volumn 23, Issue 1, 2016, Pages 60-76

  Hering, Bernhard J ^a   O'Connell, Philip J ^b  

^a UNIVERSITY OF MINNESOTA MEDICAL SCHOOL   (United States)

^b UNIVERSITY OF SYDNEY   (Australia)

Author keywords

porcine islets of Langerhans; problematic hypoglycemia; renal failure; type 1 diabetes; type 2 diabetes; xenotransplantation

Indexed keywords

INSULIN ASPART; INSULIN DEGLUDEC; INSULIN DETEMIR; INSULIN GLARGINE; INSULIN GLULISINE; INSULIN LISPRO;

CLINICAL TRIAL (TOPIC); DISEASE SEVERITY; END STAGE RENAL DISEASE; HUMAN; HYPOGLYCEMIA; IMMUNOSUPPRESSIVE TREATMENT; INSULIN DEPENDENT DIABETES MELLITUS; INSULIN INFUSION; NONHUMAN; OUTCOME ASSESSMENT; PANCREAS ISLET TRANSPLANTATION; PATIENT SELECTION; PIG; PRIORITY JOURNAL; PUBLIC HEALTH; RANDOMIZED CONTROLLED TRIAL (TOPIC); RECURRENT DISEASE; REVIEW; XENOTRANSPLANTATION; ANIMAL; CONSENSUS DEVELOPMENT; DIABETES MELLITUS, TYPE 1; PROCEDURES; XENOGRAFT;

ANIMALS; CLINICAL TRIALS AS TOPIC; DIABETES MELLITUS, TYPE 1; HUMANS; ISLETS OF LANGERHANS TRANSPLANTATION; PATIENT SELECTION; SWINE; TRANSPLANTATION, HETEROLOGOUS;

EID: 84960813255     PISSN: 0908665X     EISSN: 13993089     Source Type: Journal    
DOI: 10.1111/xen.12228     Document Type: Review

References (130)

1. Matsumoto S, Tan P, Baker J, et al., Clinical porcine islet xenotransplantation under comprehensive regulation. Transplant Proc 2014; 46: 1992-1995.
2. U.S.Department of Health and Human Services Food and Drug Administration Center for Biologics Evaluation and Research (CBER). Guidance for Industry: Source Animal, Product, Preclinical, and Clinical Issues Concerning the Use of Xenotransplantation Products in Humans. Available at: Http://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/Xenotransplantation/ucm074354.htm
3. European Medicines Agency (EMEA) Committee for Medicinal Products for Human Use (CHMP). Guideline on Xenogeneic Cell-Based Medicinal Products. Available at: Http://www.ema.europa.eu/docs/en-GB/document-library/Scientific-guideline/2009/12/WC500016936.pdf [accessed on 3 August 2015].
4. Health Research Council of New Zealand Gene Technology Advisory Committee. Guidelines for Preparation of Applications Involving Clinical Trials of Xenotransplantation in New Zealand. Available at: Http://www.hrc.govt.nz/sites/default/files/GTAC%20Guidelines%20for%20Preparation%20of%20Applications%20Involving%20Clinical%20Trials%20of%20Xenotransplantation%20in%20NZ.pdf [accessed on 3 August 2015].
5. U.S.Department of Health and Human Services Food and Drug Administration Center for Biologics Evaluation and Research. Considerations for the Design of Early-Phase Clinical Trials of Cellular and Gene Therapy Products: Guidance for Industry. Available at: Http://www.fda.gov/downloads/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/CellularandGeneTherapy/UCM359073.pdf [accessed on 3 August 2015].
6. Arcidiacono JA, Evdokimov E, Lee MH, et al., Regulation of xenogeneic porcine pancreatic islets. Xenotransplantation 2010; 17: 329-337.
7. O'Connell PJ,. The International Xenotransplantation Association consensus statement on conditions for undertaking clinical trials of porcine islet products in type 1 diabetes-chapter 6: Patient selection for pilot clinical trials of islet xenotransplantation. Xenotransplantation 2009; 16: 249-254.
8. Hering BJ, Cooper DK, Cozzi E, et al., The International Xenotransplantation Association consensus statement on conditions for undertaking clinical trials of porcine islet products in type 1 diabetes- executive summary. Xenotransplantation 2009; 16: 196-202.
9. Choudhary P, Rickels MR, Senior PA, et al., Evidence-informed clinical practice recommendations for treatment of type 1 diabetes complicated by problematic hypoglycemia. Diabetes Care 2015; 38: 1016-1029.
10. Yeoh E, Choudhary P, Nwokolo M, et al., Interventions that restore awareness of hypoglycemia in adults with type 1 diabetes: A systematic review and meta-analysis. Diabetes Care 2015; 38: 1592-1609.
11. Rosolowsky ET, Skupien J, Smiles AM, et al., Risk for ESRD in type 1 diabetes remains high despite renoprotection. J Am Soc Nephrol 2011; 22: 545-553.
12. Wiseman AC,. Pancreas transplant options for patients with type 1 diabetes mellitus and chronic kidney disease: Simultaneous pancreas kidney or pancreas after kidney? Curr Opin Organ Transplant 2012; 17: 80-86.
13. Lehmann R, Graziano J, Brockmann J, et al., Glycemic control in simultaneous islet-kidney vs pancreas-kidney transplantation in type 1 diabetes mellitus: A prospective 13 year follow-up. Diabetes Care 2015; 38: 752-759.
14. Hermanns N, Kulzer B, Krichbaum M, et al., Long-term effect of an education program (HyPOS) on the incidence of severe hypoglycemia in patients with type 1 diabetes. Diabetes Care 2010; 33: E36-e1656.
15. Hopkins D, Lawrence I, Mansell P, et al., Improved biomedical and psychological outcomes 1 year after structured education in flexible insulin therapy for people with type 1 diabetes: The U.K. DAFNE experience. Diabetes Care 2012; 35: 1638-1642.
16. de Zoysa N, Rogers H, Stadler M, et al., A psychoeducational program to restore hypoglycemia awareness: The DAFNE-HART pilot study. Diabetes Care 2014; 37: 863-866.
17. Little SA, Leelarathna L, Walkinshaw E, et al., Recovery of hypoglycemia awareness in long-standing type 1 diabetes: A multicenter 2 x 2 factorial randomized controlled trial comparing insulin pump with multiple daily injections and continuous with conventional glucose self-monitoring (HypoCOMPaSS). Diabetes Care 2014; 37: 2114-2122.
18. Singh SR, Ahmad F, Lal A, et al., Efficacy and safety of insulin analogues for the management of diabetes mellitus: A meta-analysis. CMAJ 2009; 180: 385-397.
19. Monami M, Marchionni N, Mannucci E,. Long-acting insulin analogues vs. NPH human insulin in type 1 diabetes. A meta-analysis. Diabetes Obes Metab 2009; 11: 372-378.
20. Tricco AC, Antony J, Khan PA, et al., Safety and effectiveness of dipeptidyl peptidase-4 inhibitors versus intermediate-acting insulin or placebo for patients with type 2 diabetes failing two oral antihyperglycaemic agents: A systematic review and network meta-analysis. BMJ Open 2014; 4: E005752.
21. Heller S, Buse J, Fisher M, et al., Insulin degludec, an ultra-longacting basal insulin, versus insulin glargine in basal-bolus treatment with mealtime insulin aspart in type 1 diabetes (BEGIN Basal-Bolus Type 1): A phase 3, randomised, open-label, treat-to-target non-inferiority trial. Lancet 2012; 379: 1489-1497.
22. Pedersen-Bjergaard U, Kristensen PL, Beck-Nielsen H, et al., Effect of insulin analogues on risk of severe hypoglycaemia in patients with type 1 diabetes prone to recurrent severe hypoglycaemia (HypoAna trial): A prospective, randomised, open-label, blinded-endpoint crossover trial. Lancet Diabetes Endocrinol 2014; 2: 553-561.
23. Pickup JC, Sutton AJ,. Severe hypoglycaemia and glycaemic control in Type 1 diabetes: Meta-analysis of multiple daily insulin injections compared with continuous subcutaneous insulin infusion. Diabet Med 2008; 25: 765-774.
24. Gimenez M, Lara M, Conget I,. Sustained efficacy of continuous subcutaneous insulin infusion in type 1 diabetes subjects with recurrent non-severe and severe hypoglycemia and hypoglycemia unawareness: A pilot study. Diabetes Technol Ther 2010; 12: 517-521.
25. Ryan EA, Germsheid J,. Use of continuous glucose monitoring system in the management of severe hypoglycemia. Diabetes Technol Ther 2009; 11: 635-639.
26. Choudhary P, Ramasamy S, Green L, et al., Real-time continuous glucose monitoring significantly reduces severe hypoglycemia in hypoglycemia-unaware patients with type 1 diabetes. Diabetes Care 2013; 36: 4160-4162.
27. Bergenstal RM, Tamborlane WV, Ahmann A, et al., Effectiveness of sensor-augmented insulin-pump therapy in type 1 diabetes. N Engl J Med 2010; 363: 311-320.
28. Choudhary P, Shin J, Wang Y, et al., Insulin pump therapy with automated insulin suspension in response to hypoglycemia: Reduction in nocturnal hypoglycemia in those at greatest risk. Diabetes Care 2011; 34: 2023-2025.
29. Bergenstal RM, Klonoff DC, Garg SK, et al., Threshold-based insulin-pump interruption for reduction of hypoglycemia. N Engl J Med 2013; 369: 224-232.
30. Ly TT, Nicholas JA, Retterath A, et al., Effect of sensor-augmented insulin pump therapy and automated insulin suspension vs standard insulin pump therapy on hypoglycemia in patients with type 1 diabetes: A randomized clinical trial. JAMA 2013; 310: 1240-1247.
31. Leelarathna L, Little SA, Walkinshaw E, et al., Restoration of self-awareness of hypoglycemia in adults with long-standing type 1 diabetes: Hyperinsulinemic-hypoglycemic clamp substudy results from the HypoCOMPaSS trial. Diabetes Care 2013; 36: 4063-4070.
32. Hermanns N, Kulzer B, Ehrmann D, et al., The effect of a diabetes education programme (PRIMAS) for people with type 1 diabetes: Results of a randomized trial. Diabetes Res Clin Pract 2013; 102: 149-157.
33. Beck RW, Raghinaru D, Wadwa RP, et al., Frequency of morning ketosis after overnight insulin suspension using an automated nocturnal predictive low glucose suspend system. Diabetes Care 2014; 37: 1224-1229.
34. Haidar A, Legault L, Messier V, et al., Comparison of dual-hormone artificial pancreas, single-hormone artificial pancreas, and conventional insulin pump therapy for glycaemic control in patients with type 1 diabetes: An open-label randomised controlled crossover trial. Lancet Diabetes Endocrinol 2015; 3: 17-26.
35. Byrne ML, Hopkins D, Littlejohn W, et al., Outcomes for adults with type 1 diabetes referred with severe hypoglycaemia and/or referred for islet transplantation to a specialist hypoglycaemia service. Horm Metab Res 2015; 47: 9-15.
36. Kendall DM, Rooney DP, Smets YF, et al., Pancreas transplantation restores epinephrine response and symptom recognition during hypoglycemia in patients with long-standing type I diabetes and autonomic neuropathy. Diabetes 1997; 46: 249-257.
37. Barrou Z, Seaquist ER, Robertson RP,. Pancreas transplantation in diabetic humans normalizes hepatic glucose production during hypoglycemia. Diabetes 1994; 43: 661-666.
38. Bolinder J, Wahrenberg H, Persson A, et al., Effect of pancreas transplantation on glucose counterregulation in insulin-dependent diabetic patients prone to severe hypoglycaemia. J Intern Med 1991; 230: 527-533.
39. Diem P, Redmon JB, Abid M, et al., Glucagon, catecholamine and pancreatic polypeptide secretion in type I diabetic recipients of pancreas allografts. J Clin Invest 1990; 86: 2008-2013.
40. Bosi E, Piatti PM, Secchi A, et al., Response of glucagon and insulin secretion to insulin-induced hypoglycemia in Type 1 diabetic patients after pancreas transplantation. Diabetes Nutr Metab 1988; 1: 21-27.
41. Rickels MR, Fuller C, Dalton-Bakes C, et al., Restoration of glucose counterregulation by islet transplantation in long-standing type 1 diabetes. Diabetes 2015; 64: 1713-1718.
42. Ang M, Meyer C, Brendel MD, et al., Magnitude and mechanisms of glucose counterregulation following islet transplantation in patients with type 1 diabetes suffering from severe hypoglycaemic episodes. Diabetologia 2014; 57: 623-632.
43. Vantyghem MC, Raverdy V, Balavoine AS, et al., Continuous glucose monitoring after islet transplantation in type 1 diabetes: An excellent graft function (beta-score greater than 7) Is required to abrogate hyperglycemia, whereas a minimal function is necessary to suppress severe hypoglycemia (beta-score greater than 3). J Clin Endocrinol Metab 2012; 97: E2078-E2083.
44. U.S.Food and Drug Administration. Guidance for Industry: Considerations for Allogeneic Pancreatic Islet Cell Products. Available at: Http://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/default.htm. 2008 [accessed on 3 August 2015].
45. Tiwari JL, Schneider B, Barton F, et al., Islet cell transplantation in type 1 diabetes: An analysis of efficacy outcomes and considerations for trial designs. Am J Transplant 2012; 12: 1898-1907.
46. Clinical Islet Transplantation Consortium. www.isletstudy.org.
47. O'Connell PJ, Holmes-Walker DJ, Goodman D, et al., Multicenter Australian trial of islet transplantation: Improving accessibility and outcomes. Am J Transplant 2013; 13: 1850-1858.
48. Brooks AM, Walker N, Aldibbiat A, et al., Attainment of metabolic goals in the integrated UK islet transplant program with locally isolated and transported preparations. Am J Transplant 2013; 13: 3236-3243.
49. Barton FB, Rickels MR, Alejandro R, et al., Improvement in outcomes of clinical islet transplantation: 1999-2010. Diabetes Care 2012; 35: 1436-1445.
50. Hering BJ, Bellin MD,. Transplantation: Sustained benefits of islet transplants for T1DM. Nat Rev Endocrinol 2015; 11: 572-574.
51. Lablanche S, Borot S, Wojtusciszyn A, et al., Five-year metabolic, functional, and safety results of patients with type 1 diabetes transplanted with allogenic islets within the Swiss-French GRAGIL network. Diabetes Care 2015; 38: 1714-1722.
52. Bellin MD, Barton FB, Heitman A, et al., Potent induction immunotherapy promotes long-term insulin independence after islet transplantation in type 1 diabetes. Am J Transplant 2012; 12: 1576-1583.
53. Thompson DM, Meloche M, Ao Z, et al., Reduced progression of diabetic microvascular complications with islet cell transplantation compared with intensive medical therapy. Transplantation 2011; 91: 373-378.
54. Lind M, Svensson AM, Kosiborod M, et al., Glycemic control and excess mortality in type 1 diabetes. N Engl J Med 2014; 371: 1972-1982.
55. Miller KM, Foster NC, Beck RW, et al., Current state of type 1 diabetes treatment in the U.S.: Updated data from the T1D Exchange clinic registry. Diabetes Care 2015; 38: 971-978.
56. Krolewski AS,. Progressive renal decline: The new paradigm of diabetic nephropathy in type 1 diabetes. Diabetes Care 2015; 38: 954-962.
57. Shapiro AM, Lakey JR, Ryan EA, et al., Islet transplantation in seven patients with type 1 diabetes mellitus using a glucocorticoid-free immunosuppressive regimen [see comments]. N Engl J Med 2000; 343: 230-238.
58. Ryan EA, Paty BW, Senior PA, et al., Five-year follow-up after clinical islet transplantation. Diabetes 2005; 54: 2060-2069.
59. Rickels MR, Schutta MH, Mueller R, et al., Islet cell hormonal responses to hypoglycemia after human islet transplantation for type 1 diabetes. Diabetes 2005; 54: 3205-3211.
60. Rickels MR, Fuller C, Dalton-Bakes C, et al., Restoration of glucose counterregulation by islet transplantation in long-standing type 1 diabetes. Diabetes 2015; 64: 1713-1718.
61. Balamurugan AN, Naziruddin B, Lockridge A, et al., Islet product characteristics and factors related to successful human islet transplantation from the Collaborative Islet Transplant Registry (CITR) 1999-2010. Am J Transplant 2014; 14: 2595-2606.
62. Menke A, Orchard TJ, Imperatore G, et al., The prevalence of type 1 diabetes in the United States. Epidemiology 2013; 24: 773-774.
63. Geddes J, Schopman JE, Zammitt NN, et al., Prevalence of impaired awareness of hypoglycaemia in adults with Type 1 diabetes. Diabet Med 2008; 25: 501-504.
64. Schulz TC, Young HY, Agulnick AD, et al., A scalable system for production of functional pancreatic progenitors from human embryonic stem cells. PLoS ONE 2012; 7: E37004.
65. Agulnick AD, Ambruzs DM, Moorman MA, et al., Insulin-producing endocrine cells differentiated in vitro from human embryonic stem cells function in macroencapsulation devices in vivo. Stem Cells Transl Med 2015; 4: 1214-1222.
66. Rezania A, Bruin JE, Arora P, et al., Reversal of diabetes with insulin-producing cells derived in vitro from human pluripotent stem cells. Nat Biotechnol 2014; 32: 1121-1133.
67. Pagliuca FW, Millman JR, Gurtler M, et al., Generation of functional human pancreatic beta cells in vitro. Cell 2014; 159: 428-439.
68. Viacyte. VC-01TM Combination Product is in the Clinic. Available at: Http://viacytecom/clinical/clinical-trials/ 2014 [accessed on 3 August 2015].
69. Emanuel EJ, Wendler D, Grady C,. What makes clinical research ethical? JAMA 2000; 283: 2701-2711.
70. Vanderpool HY,. The International Xenotransplantation Association consensus statement on conditions for undertaking clinical trials of porcine islet products in type 1 diabetes-Chapter 7: Informed consent and xenotransplantation clinical trials. Xenotransplantation 2009; 16: 255-262.
71. Fishman JA, Patience C,. Xenotransplantation: Infectious risk revisited. Am J Transplant 2004; 4: 1383-1390.
72. Sykes M, D'Apice A, Sandrin M,. Position paper of the Ethics Committee of the International Xenotransplantation Association. Xenotransplantation 2003; 10: 194-203.
73. First WHO global consultation on regulatory requirements for xenotransplantation clinical trials, Changsha, China, The Changsha Communiqué, 19-21 November 2008. 2008. Available at: Http://www.who.int/transplantation/xeno/ChangshaCommunique.pdf.pdf [accessed on 3 August 2015].
74. Food and Drug Administration Center for Biologics Evaluation and Research Cellular, Tissue and Gene Therapies Advisory Committee. Summary Minutes of Meeting #47, May 14-15, 2009: Animal Models for Porcine Islet Xenotransplantation Products Intended to Treat Type 1 Diabetes or Acute Liver Failure. Available at: Http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/BloodVaccinesandOtherBiologics/CellularTissueandGeneTherapiesAdvisoryCommittee/UCM183597.pdf 2009 [accessed on 3 August 2015].
75. Hering BJ, Wijkstrom M, Graham ML, et al., Prolonged diabetes reversal after intraportal xenotransplantation of wild-type porcine islets in immunosuppressed nonhuman primates. Nat Med 2006; 12: 301-303.
76. Cardona K, Korbutt GS, Milas Z, et al., Long-term survival of neonatal porcine islets in nonhuman primates by targeting costimulation pathways. Nat Med 2006; 12: 304-306.
77. Van Der Windt DJ, Bottino R, Casu A, et al., Long-term controlled normoglycemia in diabetic non-human primates after transplantation with hCD46 transgenic porcine islets. Am J Transplant 2009; 9: 2716-2726.
78. Hecht G, Eventov-Friedman S, Rosen C, et al., Embryonic pig pancreatic tissue for the treatment of diabetes in a nonhuman primate model. Proc Natl Acad Sci U S A 2009; 106: 8659-8664.
79. Thompson P, Cardona K, Russell M, et al., CD40-specific costimulation blockade enhances neonatal porcine islet survival in nonhuman primates. Am J Transplant 2011; 11: 947-957.
80. Thompson P, Badell IR, Lowe M, et al., Islet xenotransplantation using gal-deficient neonatal donors improves engraftment and function. Am J Transplant 2011; 11: 2593-2602.
81. Thompson P, Badell IR, Lowe M, et al., Alternative immunomodulatory strategies for xenotransplantation: CD40/154 pathway-sparing regimens promote xenograft survival. Am J Transplant 2012; 12: 1765-1775.
82. Jung KC, Park CG, Jeon YK, et al., In situ induction of dendritic cell-based T cell tolerance in humanized mice and nonhuman primates. J Exp Med 2011; 208: 2477-2488.
83. Bottino R, Wijkstrom M, van der Windt DJ, et al., Pig-to-monkey islet xenotransplantation using multi-transgenic pigs. Am J Transplant 2014; 14: 2275-2287.
84. Kang HJ, Lee H, Ha JM, et al., The role of the alternative complement pathway in early graft loss after intraportal porcine islet xenotransplantation. Transplantation 2014; 97: 999-1008.
85. Shin JS, Kim JM, Kim JS, et al., Long-term control of diabetes in immunosuppressed nonhuman primates (NHP) by the transplantation of adult porcine islets. Am J Transplant 2015; 15: 2837-2850.
86. Cooper DK, Casu A,. The International Xenotransplantation Association consensus statement on conditions for undertaking clinical trials of porcine islet products in type 1 diabetes-chapter 4: Pre-clinical efficacy and complication data required to justify a clinical trial. Xenotransplantation 2009; 16: 229-238.
87. Kawai T, Andrews D, Colvin RB, et al., Thromboembolic complications after treatment with monoclonal antibody against CD40 ligand [letter]. Nat Med 2000; 6: 114.
88. Monk NJ, Hargreaves RE, Marsh JE, et al., Fc-dependent depletion of activated T cells occurs through CD40L-specific antibody rather than costimulation blockade. Nat Med 2003; 9: 1275-1280.
89. Zirlik A, Maier C, Gerdes N, et al., CD40 ligand mediates inflammation independently of CD40 by interaction with Mac-1. Circulation 2007; 115: 1571-1580.
90. Badell IR, Thompson PW, Turner AP, et al., Nondepleting anti-CD40-based therapy prolongs allograft survival in nonhuman primates. Am J Transplant 2012; 12: 126-135.
91. Lowe M, Badell IR, Thompson P, et al., A novel monoclonal antibody to CD40 prolongs islet allograft survival. Am J Transplant 2012; 12: 2079-2087.
92. Watanabe M, Yamashita K, Suzuki T, et al., ASKP1240, a fully human anti-CD40 monoclonal antibody, prolongs pancreatic islet allograft survival in nonhuman primates. Am J Transplant 2013; 13: 1976-1988.
93. Mohiuddin MM, Singh AK, Corcoran PC, et al., One-year heterotopic cardiac xenograft survival in a pig to baboon model. Am J Transplant 2014; 14: 488-489.
94. van der Windt DJ, Bottino R, Casu A, et al., Rapid loss of intraportally transplanted islets: An overview of pathophysiology and preventive strategies. Xenotransplantation 2007; 14: 288-297.
95. Rayat GR, Rajotte RV, Hering BJ, et al., In vitro and in vivo expression of Galalpha-(1,3)Gal on porcine islet cells is age dependent. J Endocrinol 2003; 177: 127-135.
96. Phelps CJ, Koike C, Vaught TD, et al., Production of alpha 1,3-galactosyltransferase-deficient pigs. Science 2003; 299: 411-414.
97. Hawthorne WJ, Salvaris EJ, Phillips P, et al., Control of IBMIR in neonatal porcine islet xenotransplantation in baboons. Am J Transplant 2014; 14: 1300-1309.
98. Dufrane D, Goebbels RM, Gianello P,. Alginate macroencapsulation of pig islets allows correction of streptozotocin-induced diabetes in primates up to 6 months without immunosuppression. Transplantation 2010; 90: 1054-1062.
99. Veriter S, Gianello P, Igarashi Y, et al., Improvement of subcutaneous bioartificial pancreas vascularization and function by coencapsulation of pig islets and mesenchymal stem cells in primates. Cell Transplant 2014; 23: 1349-1364.
100. Ludwig B, Reichel A, Steffen A, et al., Transplantation of human islets without immunosuppression. Proc Natl Acad Sci USA 2013; 110: 19054-19058.
101. Neufeld T, Ludwig B, Barkai U, et al., The efficacy of an immunoisolating membrane system for islet xenotransplantation in minipigs. PLoS ONE 2013; 8: E70150.
102. Garkavenko O, Durbin K, Tan P, Elliott R,. Islets transplantation: New Zealand experience. Xenotransplantation 2011; 18: 60.
103. Living Cell Technologies. Diabecell-development to date. Available at: Http://www.lctglobal.com/products/diabecell/development-to-date [accessed on 16 February 2015].
104. Wynyard S, Nathu D, Garkavenko O, et al., Microbiological safety of the first clinical pig islet xenotransplantation trial in New Zealand. Xenotransplantation 2014; 21: 309-323.
105. Bartlett ST, Markmann JF, Johnson P, et al., Report from IPITA-TTS opinion leaders meeting on the future of beta-cell replacement. Transplantation 2016; 100 (Suppl. 2): S1-S44.
106. Astellas Pharma Global Development I. A study to assess the efficacy and safety of ASKP1240 in de novo kidney transpant recipients. Available at: Https://clinicaltrials.gov/ct2/show/NCT01780844?term=anti-cd40+kidney+transplantation&rank=3 2013 [accessed on 3 August 2015].
107. Novartis Pharmaceuticals. CCFZ533X2201-PoC Study in de Novo Renal Transplantation. Available at: Https://clinicaltrials.gov/ct2/show/NCT02217410?term=anti-cd40+kidney+transplantation&rank=2 2014 [accessed on 3 August 2015].
108. Samy KP, Martin BM, Turgeon NA, et al., Islet cell xenotransplantation: A serious look toward the clinic. Xenotransplantation 2014; 21: 221-229.
109. Lutz AJ, Li P, Estrada JL, et al., Double knockout pigs deficient in N-glycolylneuraminic acid and galactose alpha-1,3-galactose reduce the humoral barrier to xenotransplantation. Xenotransplantation 2013; 20: 27-35.
110. Burlak C, Paris LL, Lutz AJ, et al., Reduced binding of human antibodies to cells from GGTA1/CMAH KO pigs. Am J Transplant 2014; 14: 1895-1900.
111. Byrne GW, Du Z, Stalboerger P, et al., Cloning and expression of porcine beta1,4 N-acetylgalactosaminyl transferase encoding a new xenoreactive antigen. Xenotransplantation 2014; 21: 543-554.
112. Estrada JL, Martens G, Li P, et al., Evaluation of human and non-human primate antibody binding to pig cells lacking GGTA1/CMAH/beta4GalNT2 genes. Xenotransplantation 2015; 22: 194-202.
113. Wong BS, Yamada K, Okumi M, et al., Allosensitization does not increase the risk of xenoreactivity to alpha1,3-galactosyltransferase gene-knockout miniature swine in patients on transplantation waiting lists. Transplantation 2006; 82: 314-319.
114. Hara H, Ezzelarab M, Rood PP, et al., Allosensitized humans are at no greater risk of humoral rejection of GT-KO pig organs than other humans. Xenotransplantation 2006; 13: 357-365.
115. Mulder A, Kardol MJ, Arn JS, et al., Human monoclonal HLA antibodies reveal interspecies crossreactive swine MHC class I epitopes relevant for xenotransplantation. Mol Immunol 2010; 47: 809-815.
116. Schopman JE, Geddes J, Frier BM,. Prevalence of impaired awareness of hypoglycaemia and frequency of hypoglycaemia in insulin-treated type 2 diabetes. Diabetes Res Clin Pract 2010; 87: 64-68.
117. Higginbotham L, Mathews D, Breeden CA, et al., Pre-transplant antibody screening and anti-CD154 costimulation blockade promote long-term xenograft survival in a pig-to-primate kidney transplant model. Xenotransplantation 2015; 22: 221-230.
118. Iwase H, Liu H, Wijkstrom M, et al., Pig kidney graft survival in a baboon for 136 days: Longest life-supporting organ graft survival to date. Xenotransplantation 2015; 22: 302-309.
119. Ciancio G, Burke GW,. Type 2 diabetes: Is pancreas transplantation an option? Curr Diab Rep 2014; 14: 542.
120. Weems P, Cooper M,. Pancreas transplantation in type II diabetes mellitus. World J Transplant 2014; 4: 216-221.
121. Ryan EA, Shandro T, Green K, et al., Assessment of the severity of hypoglycemia and glycemic lability in type 1 diabetic subjects undergoing islet transplantation. Diabetes 2004; 53: 955-962.
122. Gall FP, Muhe E, Gebhardt C,. Results of partial and total pancreaticoduodenectomy in 117 patients with chronic pancreatitis. World J Surg 1981; 5: 269-275.
123. Dresler CM, Fortner JG, McDermott K, et al., Metabolic consequences of (regional) total pancreatectomy. Ann Surg 1991; 214: 131-140.
124. Cooper MJ, Williamson RC, Benjamin IS, et al., Total pancreatectomy for chronic pancreatitis. Br J Surg 1987; 74: 912-915.
125. Sarr MG, Behrns KE, Van Heerden JA,. Total pancreatectomy. An objective analysis of its use in pancreatic cancer. Hepatogastroenterology 1993; 40: 418-421.
126. Ihse I, Anderson H, Andren S,. Total pancreatectomy for cancer of the pancreas: Is it appropriate? World J Surg 1996; 20: 288-293.
127. Gruessner RW, Sutherland DE, Drangstveit MB, et al., Pancreas allotransplants in patients with a previous total pancreatectomy for chronic pancreatitis. J Am Coll Surg 2008; 206: 458-465.
128. Li P, Estrada JL, Burlak C, et al., Efficient generation of genetically distinct pigs in a single pregnancy using multiplexed single-guide RNA and carbohydrate selection. Xenotransplantation 2015; 22: 20-31.
129. Wang S, Tasch J, Kheradmand T, et al., Transient B-cell depletion combined with apoptotic donor splenocytes induces xeno-specific T- and B-cell tolerance to islet xenografts. Diabetes 2013; 62: 3143-3150.
130. Kalscheuer H, Onoe T, Dahmani A, et al., Xenograft tolerance and immune function of human T cells developing in pig thymus xenografts. J Immunol 2014; 192: 3442-3450.