Update on Islet Cell Transplantation for Type 1 Diabetes

 

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Abstract

Despite modern medical breakthroughs, diabetes mellitus is a worldwide leading cause of morbidity and mortality. Definitive surgical treatment of diabetes mellitus was established with the advent and refinement of clinical pancreas transplantation in the 1960s. During the following decades, critical discoveries involving islet isolation and engraftment took place. Clinical islet cell transplantation represents the potential for reduced insulin requirements and debilitating hypoglycemic episodes without the morbidity of surgery. Unfortunately, islet cell transplantation was unable to achieve comparable results with solid organ transplantation. This was until the Edmonton protocol (steroid-free immunosuppression) was described, which demonstrated that islet cell transplantation could be a viable alternative to pancreas transplantation. Significant advances in islet purification techniques and novel immunomodulatory agents have since renewed interest in islet cell transplantation. Yet the field is still challenged by a limited supply of islet cells, inadequate engraftment, and the deleterious effects of chronic immunosuppression. This article discusses the history and the current status of clinical islet cell transplantation.

• References

• 1 Gepts W. Islet morphology in type I diabetes. Behring Inst Mitt 1984; (75) 39-41
  PubMedGoogle Scholar
• 2 Atkinson MA, Eisenbarth GS. Type 1 diabetes: new perspectives on disease pathogenesis and treatment. Lancet 2001; 358 (9277) 221-229
  CrossrefPubMedGoogle Scholar
• 3 Larsen CE, Alper CA. The genetics of HLA-associated disease. Curr Opin Immunol 2004; 16 (5) 660-667
  CrossrefPubMedGoogle Scholar
• 4 Knip M. Environmental triggers and determinants of beta-cell autoimmunity and type 1 diabetes. Rev Endocr Metab Disord 2003; 4 (3) 213-223
  CrossrefPubMedGoogle Scholar
• 5 Bruno G, Landi A. Epidemiology and costs of diabetes. Transplant Proc 2011; 43 (1) 327-329
  CrossrefPubMedGoogle Scholar
• 6 Rubin RJ, Altman WM, Mendelson DN. Health care expenditures for people with diabetes mellitus, 1992. J Clin Endocrinol Metab 1994; 78 (4) 809A-809F
  CrossrefPubMedGoogle Scholar
• 7 American Diabetes Association Task Force for Writing Nutrition Principles and Recommendations for the Management of Diabetes and Related Complications. American Diabetes Association position statement: evidence-based nutrition principles and recommendations for the treatment and prevention of diabetes and related complications. J Am Diet Assoc 2002; 102 (1) 109-118
  CrossrefPubMedGoogle Scholar
• 8 Banting FG, Best CH, Collip JB, Campbell WR, Fletcher AA. Pancreatic extracts in the treatment of diabetes mellitus. Can Med Assoc J 1922; 12 (3) 141-146
  PubMedGoogle Scholar
• 9 The Diabetes Control and Complications Trial Research Group. Hypoglycemia in the Diabetes Control and Complications Trial. Diabetes 1997; 46 (2) 271-286
  CrossrefPubMedGoogle Scholar
• 10 von Mering J, Minkowski O. Diabetes mellitus after pancreas extirpation. Arch Exp Pathol Pharmakol 1889; 26: 111
  PubMedGoogle Scholar
• 11 Kelly WD, Lillehei RC, Merkel FK, Idezuki Y, Goetz FC. Allotransplantation of the pancreas and duodenum along with the kidney in diabetic nephropathy. Surgery 1967; 61 (6) 827-837
  PubMedGoogle Scholar
• 12 Gruessner AC, Sutherland DE. Pancreas transplant outcomes for United States (US) and non-US cases as reported to the United Network for Organ Sharing (UNOS) and the International Pancreas Transplant Registry (IPTR) as of June 2004. Clin Transplant 2005; 19 (4) 433-455
  CrossrefPubMedGoogle Scholar
• 13 Sutherland DE, Gruessner RW, Dunn DL , et al. Lessons learned from more than 1,000 pancreas transplants at a single institution. Ann Surg 2001; 233 (4) 463-501
  CrossrefPubMedGoogle Scholar
• 14 Lacy PE, Kostianovsky M. Method for the isolation of intact islets of Langerhans from the rat pancreas. Diabetes 1967; 16 (1) 35-39
  CrossrefPubMedGoogle Scholar
• 15 Kemp CB, Knight MJ, Scharp DW, Ballinger WF, Lacy PE. Effect of transplantation site on the results of pancreatic islet isografts in diabetic rats. Diabetologia 1973; 9 (6) 486-491
  CrossrefPubMedGoogle Scholar
• 16 Scharp DW, Kemp CB, Knight MJ, Ballinger WF, Lacy PE. The use of ficoll in the preparation of viable islets of Langerhans from the rat pancreas. Transplantation 1973; 16 (6) 686-689
  CrossrefPubMedGoogle Scholar
• 17 Najarian JS, Sutherland DE, Matas AJ, Steffes MW, Simmons RL, Goetz FC. Human islet transplantation: a preliminary report. Transplant Proc 1977; 9 (1) 233-236
  PubMedGoogle Scholar
• 18 Largiadèr F, Kolb E, Binswanger U. A long-term functioning human pancreatic islet allotransplant. Transplantation 1980; 29 (1) 76-77
  CrossrefPubMedGoogle Scholar
• 19 Tzakis AG, Ricordi C, Alejandro R , et al. Pancreatic islet transplantation after upper abdominal exenteration and liver replacement. Lancet 1990; 336 (8712) 402-405
  CrossrefPubMedGoogle Scholar
• 20 Oberholzer J, Triponez F, Mage R , et al. Human islet transplantation: lessons from 13 autologous and 13 allogeneic transplantations. Transplantation 2000; 69 (6) 1115-1123
  CrossrefPubMedGoogle Scholar
• 21 Socci C, Falqui L, Davalli AM , et al. Allotransplantation of fresh islets in four type I diabetic patients. Transplant Proc 1992; 24 (3) 965-966
  PubMedGoogle Scholar
• 22 Brendel M, Hering B, Schulz A, Bretzel R. International Islet Transplant Registry report. Glessen, Germany: University of Glessen; 1999: 1-20
  Google Scholar
• 23 Shapiro AJ, Lakey JT , et al. Islet transplantation in seven patients with type 1 diabetes mellitus using a glucocorticoid-free immunosuppressive regimen. N Engl J Med 2000; 343 (4) 230-238
  CrossrefPubMedGoogle Scholar
• 24 Cure P, Pileggi A, Froud T , et al. Improved metabolic control and quality of life in seven patients with type 1 diabetes following islet after kidney transplantation. Transplantation 2008; 85 (6) 801-812
  CrossrefPubMedGoogle Scholar
• 25 Fiorina P, Venturini M, Folli F , et al. Natural history of kidney graft survival, hypertrophy, and vascular function in end-stage renal disease type 1 diabetic kidney-transplanted patients: beneficial impact of pancreas and successful islet cotransplantation. Diabetes Care 2005; 28 (6) 1303-1310
  CrossrefPubMedGoogle Scholar
• 26 Zeng Y, Torre MA, Karrison T, Thistlethwaite JR. The correlation between donor characteristics and the success of human islet isolation. Transplantation 1994; 57 (6) 954-958
  CrossrefPubMedGoogle Scholar
• 27 Ricordi C. Quantitative and qualitative standards for islet isolation assessment in humans and large mammals. Pancreas 1991; 6 (2) 242-244
  CrossrefPubMedGoogle Scholar
• 28 Brandhorst H, Brandhorst D, Hering BJ, Federlin K, Bretzel RG. Body mass index of pancreatic donors: a decisive factor for human islet isolation. Exp Clin Endocrinol Diabetes 1995; 103 (Suppl. 02) 23-26
  Article in Thieme ConnectPubMedGoogle Scholar
• 29 Ricordi C, Lacy PE, Finke EH, Olack BJ, Scharp DW. Automated method for isolation of human pancreatic islets. Diabetes 1988; 37 (4) 413-420
  CrossrefPubMedGoogle Scholar
• 30 Kin T, Johnson PR, Shapiro AM, Lakey JR. Factors influencing the collagenase digestion phase of human islet isolation. Transplantation 2007; 83 (1) 7-12
  CrossrefPubMedGoogle Scholar
• 31 Kin T, Zhai X, Murdoch TB, Salam A, Shapiro AM, Lakey JR. Enhancing the success of human islet isolation through optimization and characterization of pancreas dissociation enzyme. Am J Transplant 2007; 7 (5) 1233-1241
  CrossrefPubMedGoogle Scholar
• 32 Olack BJ, Swanson CJ, Howard TK, Mohanakumar T. Improved method for the isolation and purification of human islets of Langerhans using Liberase enzyme blend. Hum Immunol 1999; 60 (12) 1303-1309
  CrossrefPubMedGoogle Scholar
• 33 Alejandro R, Barton FB, Hering BJ, Wease S ; Collaborative Islet Transplant Registry Investigators. 2008 Update from the Collaborative Islet Transplant Registry. Transplantation 2008; 86 (12) 1783-1788
  CrossrefPubMedGoogle Scholar
• 34 Caballero-Corbalan J, Brandhorst H, Asif S, Korsgren O, Engelse M, de Koning E , et al. Mammalian tissue-free liberase: a new GMP-graded enzyme blend for human islet isolation. Transplantation 2010; 90 (3) 332-333
  PubMedGoogle Scholar
• 35 Caballero-Corbalán J, Friberg AS, Brandhorst H , et al. Vitacyte collagenase HA: a novel enzyme blend for efficient human islet isolation. Transplantation 2009; 88 (12) 1400-1402
  CrossrefPubMedGoogle Scholar
• 36 Szot GL, Lee MR, Tavakol MM , et al. Successful clinical islet isolation using a GMP-manufactured collagenase and neutral protease. Transplantation 2009; 88 (6) 753-756
  CrossrefPubMedGoogle Scholar
• 37 Goto M, Eich TM, Felldin M , et al. Refinement of the automated method for human islet isolation and presentation of a closed system for in vitro islet culture. Transplantation 2004; 78 (9) 1367-1375
  CrossrefPubMedGoogle Scholar
• 38 Abdelli S, Ansite J, Roduit R , et al. Intracellular stress signaling pathways activated during human islet preparation and following acute cytokine exposure. Diabetes 2004; 53 (11) 2815-2823
  CrossrefPubMedGoogle Scholar
• 39 Bottino R, Balamurugan AN, Tse H , et al. Response of human islets to isolation stress and the effect of antioxidant treatment. Diabetes 2004; 53 (10) 2559-2568
  CrossrefPubMedGoogle Scholar
• 40 Murdoch TB, McGhee-Wilson D, Shapiro AM, Lakey JR. Methods of human islet culture for transplantation. Cell Transplant 2004; 13 (6) 605-617
  CrossrefPubMedGoogle Scholar
• 41 Venturini M, Angeli E, Maffi P , et al. Technique, complications, and therapeutic efficacy of percutaneous transplantation of human pancreatic islet cells in type 1 diabetes: the role of US. Radiology 2005; 234 (2) 617-624
  CrossrefPubMedGoogle Scholar
• 42 Baidal DA, Froud T, Ferreira JV, Khan A, Alejandro R, Ricordi C. The bag method for islet cell infusion. Cell Transplant 2003; 12 (7) 809-813
  PubMedGoogle Scholar
• 43 Saad W, Maddoff D. Percutaneous portal vein access and transhepatic tract hemostasis. Semin Intervent Radiol 2012; 29 (2) 71-80
  Article in Thieme ConnectPubMedGoogle Scholar
• 44 Casey JJ, Lakey JR, Ryan EA , et al. Portal venous pressure changes after sequential clinical islet transplantation. Transplantation 2002; 74 (7) 913-915
  CrossrefPubMedGoogle Scholar
• 45 Ryan EA, Paty BW, Senior PA, Shapiro AM. Risks and side effects of islet transplantation. Curr Diab Rep 2004; 4 (4) 304-309
  CrossrefPubMedGoogle Scholar
• 46 Moberg L, Johansson H, Lukinius A , et al. Production of tissue factor by pancreatic islet cells as a trigger of detrimental thrombotic reactions in clinical islet transplantation. Lancet 2002; 360 (9350) 2039-2045
  CrossrefPubMedGoogle Scholar
• 47 Johansson H, Lukinius A, Moberg L , 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 (6) 1755-1762
  CrossrefPubMedGoogle Scholar
• 48 Kawahara T, Kin T, Kashkoush S, Gala-Lopez B, Bigam DL, Kneteman NM , et al. Portal vein thrombosis is a potentially preventable complication in clinical islet transplantation. Am J Transplant 2011; 11 (12) 2700-2707
  CrossrefPubMedGoogle Scholar
• 49 Kawahara T, Kin T, Shapiro AM. A comparison of islet autotransplantation with allotransplantation and factors elevating acute portal pressure in clinical islet transplantation. J Hepatobiliary Pancreat Sci 2012; 19 (3) 281-288
  CrossrefPubMedGoogle Scholar
• 50 Johansson H, Goto M, Dufrane D , et al. Low molecular weight dextran sulfate: a strong candidate drug to block IBMIR in clinical islet transplantation. Am J Transplant 2006; 6 (2) 305-312
  CrossrefPubMedGoogle Scholar
• 51 Cabric S, Sanchez J, Lundgren T , et al. Islet surface heparinization prevents the instant blood-mediated inflammatory reaction in islet transplantation. Diabetes 2007; 56 (8) 2008-2015
  CrossrefPubMedGoogle Scholar
• 52 Berney T, Secchi A. Rapamycin in islet transplantation: friend or foe?. Transpl Int 2009; 22 (2) 153-161
  CrossrefPubMedGoogle Scholar
• 53 Ryan EA, Paty BW, Senior PA , et al. Five-year follow-up after clinical islet transplantation. Diabetes 2005; 54 (7) 2060-2069
  CrossrefPubMedGoogle Scholar
• 54 Kenmochi T, Asano T, Maruyama M , et al. Clinical islet transplantation in Japan. J Hepatobiliary Pancreat Surg 2009; 16 (2) 124-130
  CrossrefPubMedGoogle Scholar
• 55 Papas KK, Avgoustiniatos ES, Tempelman LA , et al. High-density culture of human islets on top of silicone rubber membranes. Transplant Proc 2005; 37 (8) 3412-3414
  CrossrefPubMedGoogle Scholar
• 56 Koh A, Senior P, Salam A, Kin T, Imes S, Dinyari P , et al. Insulin-heparin infusions peritransplant substantially improve single-donor clinical islet transplant success. Transplantation 2010; 89 (4) 465-471
  CrossrefPubMedGoogle Scholar
• 57 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 (1) 48-55
  CrossrefPubMedGoogle Scholar
• 58 Faradji RN, Tharavanij T, Messinger S , et al. Long-term insulin independence and improvement in insulin secretion after supplemental islet infusion under exenatide and etanercept. Transplantation 2008; 86 (12) 1658-1665
  CrossrefPubMedGoogle Scholar
• 59 Gangemi A, Salehi P, Hatipoglu B , et al. Islet transplantation for brittle type 1 diabetes: the UIC protocol. Am J Transplant 2008; 8 (6) 1250-1261
  CrossrefPubMedGoogle Scholar
• 60 Low G, Hussein N, Owen RJ, Toso C, Patel VH, Bhargava R , et al. Role of imaging in clinical islet transplantation. Radiographics 2010; 30 (2) 353-366
  CrossrefPubMedGoogle Scholar
• 61 Eich T, Eriksson O, Lundgren T ; Nordic Network for Clinical Islet Transplantation. Visualization of early engraftment in clinical islet transplantation by positron-emission tomography. N Engl J Med 2007; 356 (26) 2754-2755
  CrossrefPubMedGoogle Scholar
• 62 Tai JH, Foster P, Rosales A , et al. Imaging islets labeled with magnetic nanoparticles at 1.5 Tesla. Diabetes 2006; 55 (11) 2931-2938
  CrossrefPubMedGoogle Scholar
• 63 Toso C, Vallee JP, Morel P , et al. Clinical magnetic resonance imaging of pancreatic islet grafts after iron nanoparticle labeling. Am J Transplant 2008; 8 (3) 701-706
  CrossrefPubMedGoogle Scholar
• 64 Jirák D, Kríz J, Herynek V , et al. MRI of transplanted pancreatic islets. Magn Reson Med 2004; 52 (6) 1228-1233
  CrossrefPubMedGoogle Scholar
• 65 Aguayo-Mazzucato C, Bonner-Weir S. Stem cell therapy for type 1 diabetes mellitus. Nat Rev Endocrinol 2010; 6 (3) 139-148
  CrossrefPubMedGoogle Scholar
• 66 Furth ME, Atala A. Stem cell sources to treat diabetes. J Cell Biochem 2009; 106 (4) 507-511
  CrossrefPubMedGoogle Scholar
• 67 D'Amour KA, Bang AG, Eliazer S , et al. Production of pancreatic hormone-expressing endocrine cells from human embryonic stem cells. Nat Biotechnol 2006; 24 (11) 1392-1401
  CrossrefPubMedGoogle Scholar
• 68 Kroon E, Martinson LA, Kadoya K , et al. Pancreatic endoderm derived from human embryonic stem cells generates glucose-responsive insulin-secreting cells in vivo. Nat Biotechnol 2008; 26 (4) 443-452
  CrossrefPubMedGoogle Scholar
• 69 Volarevic V, Arsenijevic N, Lukic ML, Stojkovic M. Concise review: Mesenchymal stem cell treatment of the complications of diabetes mellitus. Stem Cells 2011; 29 (1) 5-10
  CrossrefPubMedGoogle Scholar
• 70 Boumaza I, Srinivasan S, Witt WT , et al. Autologous bone marrow-derived rat mesenchymal stem cells promote PDX-1 and insulin expression in the islets, alter T cell cytokine pattern and preserve regulatory T cells in the periphery and induce sustained normoglycemia. J Autoimmun 2009; 32 (1) 33-42
  CrossrefPubMedGoogle Scholar
• 71 Zhang D, Jiang W, Liu M , et al. Highly efficient differentiation of human ES cells and iPS cells into mature pancreatic insulin-producing cells. Cell Res 2009; 19 (4) 429-438
  CrossrefPubMedGoogle Scholar
• 72 Slezak LA, Andersen DK. Pancreatic resection: effects on glucose metabolism. World J Surg 2001; 25 (4) 452-460
  CrossrefPubMedGoogle Scholar
• 73 Sutherland DE, Matas AJ, Najarian JS. Pancreatic islet cell transplantation. Surg Clin North Am 1978; 58 (2) 365-382
  PubMedGoogle Scholar
• 74 Ruggenenti P, Remuzzi A, Remuzzi G. Decision time for pancreatic islet-cell transplantation. Lancet 2008; 371 (9616) 883-884
  CrossrefPubMedGoogle Scholar
• 75 Sutherland DE, Gruessner AC, Carlson AM , et al. Islet autotransplant outcomes after total pancreatectomy: a contrast to islet allograft outcomes. Transplantation 2008; 86 (12) 1799-1802
  CrossrefPubMedGoogle Scholar
• 76 Kobayashi T, Manivel JC, Carlson AM , et al. Correlation of histopathology, islet yield, and islet graft function after islet autotransplantation in chronic pancreatitis. Pancreas 2011; 40 (2) 193-199
  CrossrefPubMedGoogle Scholar
• 77 Blondet JJ, Carlson AM, Kobayashi T , et al. The role of total pancreatectomy and islet autotransplantation for chronic pancreatitis. Surg Clin North Am 2007; 87 (6) 1477-1501 , x
  CrossrefPubMedGoogle Scholar
• 78 Ahmad SA, Lowy AM, Wray CJ , et al. Factors associated with insulin and narcotic independence after islet autotransplantation in patients with severe chronic pancreatitis. J Am Coll Surg 2005; 201 (5) 680-687
  CrossrefPubMedGoogle Scholar
• 79 Bellin MD, Carlson AM, Kobayashi T , et al. Outcome after pancreatectomy and islet autotransplantation in a pediatric population. J Pediatr Gastroenterol Nutr 2008; 47 (1) 37-44
  CrossrefPubMedGoogle Scholar
• 80 Bellin MD, Blondet JJ, Beilman GJ , et al. Predicting islet yield in pediatric patients undergoing pancreatectomy and autoislet transplantation for chronic pancreatitis. Pediatr Diabetes 2010; 11 (4) 227-234
  PubMedGoogle Scholar
• 81 Takita M, Naziruddin B, Matsumoto S , et al. Variables associated with islet yield in autologous islet cell transplantation for chronic pancreatitis. Proc (Bayl Univ Med Cent) 2010; 23 (2) 115-120
  PubMedGoogle Scholar