Skip to main content

Successes and Disappointments with Clinical Islet Transplantation

  • Reference work entry
  • First Online:
Islets of Langerhans

Abstract

Islet transplantation is considered a therapeutic option for patients with type 1 diabetes who have life-threatening hypoglycemic episodes. After the procedure, the frequency and severity of hypoglycemic episodes generally decrease and the majority of patients have sustained graft function as indicated by detectable levels of C-peptide. However, true insulin independence is seldom achieved and generally not long-lasting. Apart from the low insulin-independence rates, reasons for concern regarding this procedure are the side effects of the immunosuppressive therapy, alloimmunization, and the high costs. Moreover, whether islet transplantation prevents the progression of diabetic micro- and macrovascular complications more effectively than standard insulin therapy is largely unknown. Areas of current research include the development of less toxic immunosuppressive regimens, the control of the inflammatory reaction immediately after transplantation, the identification of the optimal anatomical site for islet infusion, and the possibility to encapsulate transplanted islets to protect them from the alloimmune response. Nowadays, islet transplantation is still an experimental procedure, which is only indicated for a highly selected group of type 1 diabetic patients with life-threatening hypoglycemic episodes.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 699.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 549.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

References

  • Alejandro R, Barton FB, Hering BJ, Wease S (2008) 2008 update from the Collaborative Islet Transplant Registry. Transplantation 86:1783–1788

    PubMed  Google Scholar 

  • Aviv V, Meivar-Levy I, Rachmut IH, Rubinek T, Mor E, Ferber S (2009) Exendin-4 promotes liver cell proliferation and enhances the PDX-1-induced liver to pancreas transdifferentiation process. J Biol Chem 284:33509–33520

    PubMed  CAS  PubMed Central  Google Scholar 

  • Badet L, Benhamou PY, Wojtusciszyn A et al (2007) Expectations and strategies regarding islet transplantation: metabolic data from the GRAGIL 2 trial. Transplantation 84:89–96

    PubMed  CAS  Google Scholar 

  • Ballinger WF, Lacy PE (1972) Transplantation of intact pancreatic islets in rats. Surgery 72:175–186

    PubMed  CAS  Google Scholar 

  • Barton FB, Rickels MR, Alejandro R et al (2012) Improvement in outcomes of clinical islet transplantation: 1999–2010. Diabetes Care 35:1436–1445

    PubMed  CAS  PubMed Central  Google Scholar 

  • Basta G, Montanucci P, Luca G et al (2011) Long-term metabolic and immunological follow-up of nonimmunosuppressed patients with type 1 diabetes treated with microencapsulated islet allografts: four cases. Diabetes Care 34:2406–2409

    PubMed  CAS  PubMed Central  Google Scholar 

  • Beck J, Angus R, Madsen B, Britt D, Vernon B, Nguyen KT (2007) Islet encapsulation: strategies to enhance islet cell functions. Tissue Eng 13:589–599

    PubMed  CAS  Google Scholar 

  • Beckwith J, Nyman JA, Flanagan B, Schrover R, Schuurman HJ (2012) A health economic analysis of clinical islet transplantation. Clin Transplant 26:23–33

    PubMed  Google Scholar 

  • Benhamou PY, Oberholzer J, Toso C et al (2001) Human islet transplantation network for the treatment of Type I diabetes: first data from the Swiss-French GRAGIL consortium (1999–2000). Groupe de Recherche Rhin Rhjne Alpes Geneve pour la transplantation d’Ilots de Langerhans. Diabetologia 44:859–864

    PubMed  CAS  Google Scholar 

  • Bergenstal RM, Klonoff DC, Garg SK et al (2013) Threshold-based insulin-pump interruption for reduction of hypoglycemia. N Engl J Med 369(3):224–232

    PubMed  CAS  Google Scholar 

  • Berney T, Secchi A (2009) Rapamycin in islet transplantation: friend or foe? Transpl Int 22:153–161

    PubMed  CAS  Google Scholar 

  • Berney T, Ferrari-Lacraz S, Buhler L et al (2009) Long-term insulin-independence after allogeneic islet transplantation for type 1 diabetes: over the 10-year mark. Am J Transplant 9:419–423

    PubMed  CAS  Google Scholar 

  • Bhargava R, Senior PA, Ackerman TE et al (2004) Prevalence of hepatic steatosis after islet transplantation and its relation to graft function. Diabetes 53:1311–1317

    PubMed  CAS  Google Scholar 

  • Bianco P, Cao X, Frenette PS et al (2013) The meaning, the sense and the significance: translating the science of mesenchymal stem cells into medicine. Nat Med 19:35–42

    PubMed  CAS  PubMed Central  Google Scholar 

  • Bluestone JA, Herold K, Eisenbarth G (2010) Genetics, pathogenesis and clinical interventions in type 1 diabetes. Nature 464:1293–1300

    PubMed  CAS  Google Scholar 

  • Boggi U, Vistoli F, Egidi FM et al (2012) Transplantation of the pancreas. Curr Diab Rep 12:568–579

    PubMed  CAS  Google Scholar 

  • Bonner-Weir S, Taneja M, Weir GC et al (2000) In vitro cultivation of human islets from expanded ductal tissue. Proc Natl Acad Sci U S A 97:7999–8004

    PubMed  CAS  PubMed Central  Google Scholar 

  • Braasch JW, Vito L, Nugent FW (1978) Total pancreatectomy of end-stage chronic pancreatitis. Ann Surg 188:317–322

    PubMed  CAS  PubMed Central  Google Scholar 

  • Brendel M, Hering B, Schulz A, Bretzel R (1999) International islet transplant registry report. University of Giessen, Giessen, pp 1–20

    Google Scholar 

  • Cabric S, Sanchez J, Lundgren T et al (2007) Islet surface heparinization prevents the instant blood-mediated inflammatory reaction in islet transplantation. Diabetes 56:2008–2015

    PubMed  CAS  Google Scholar 

  • Campbell PM, Senior PA, Salam A et al (2007a) High risk of sensitization after failed islet transplantation. Am J Transplant 7:2311–2317

    PubMed  CAS  Google Scholar 

  • Campbell PM, Salam A, Ryan EA et al (2007b) Pretransplant HLA antibodies are associated with reduced graft survival after clinical islet transplantation. Am J Transplant 7:1242–1248

    PubMed  CAS  Google Scholar 

  • Cardani R, Pileggi A, Ricordi C et al (2007) Allosensitization of islet allograft recipients. Transplantation 84:1413–1427

    PubMed  Google Scholar 

  • Chase HP, Cuthbertson DD, Dolan LM et al (2001) First-phase insulin release during the intravenous glucose tolerance test as a risk factor for type 1 diabetes. J Pediatr 138:244–249

    PubMed  CAS  Google Scholar 

  • Chatenoud L, Bluestone JA (2007) CD3-specific antibodies: a portal to the treatment of autoimmunity. Nat Rev Immunol 7:622–632

    PubMed  CAS  Google Scholar 

  • Chen S, Borowiak M, Fox JL et al (2009) A small molecule that directs differentiation of human ESCs into the pancreatic lineage. Nat Chem Biol 5:258–265

    PubMed  CAS  Google Scholar 

  • Claiborn KC, Stoffers DA (2008) Toward a cell-based cure for diabetes: advances in production and transplant of β cells. Mt Sinai J Med 75:362–371

    PubMed  Google Scholar 

  • Collaborative Islet Transplantation Registry (2010) Seventh annual report. http://citregistry.com Accessed on April 28, 2014

  • Coppieters KT, Wiberg A, Tracy SM, von Herrath MG (2012) Immunology in the clinic review series: focus on type 1 diabetes and viruses: the role of viruses in type 1 diabetes: a difficult dilemma. Clin Exp Immunol 168:5–11

    PubMed  CAS  PubMed Central  Google Scholar 

  • Cornolti R, Figliuzzi M, Remuzzi A (2009) Effect of micro- and macroencapsulation on oxygen consumption by pancreatic islets. Cell Transplant 18:195–201

    PubMed  Google Scholar 

  • Couri CE, Oliveira MC, Stracieri AB et al (2009) C-peptide levels and insulin independence following autologous nonmyeloablative hematopoietic stem cell transplantation in newly diagnosed type 1 diabetes mellitus. JAMA 301:1573–1579

    PubMed  CAS  Google Scholar 

  • Cravedi P, Mannon RB, Ruggenenti P, Remuzzi A, Remuzzi G (2008) Islet transplantation: need for a time-out? Nat Clin Pract Nephrol 4:660–661

    PubMed  Google Scholar 

  • Daneman D (2009) State of the world’s children with diabetes. Pediatr Diabetes 10:120–126

    PubMed  Google Scholar 

  • Danielson KK, Hatipoglu B, Kinzer K et al (2012) Reduction in carotid intima-media thickness after pancreatic islet transplantation in patients with type 1 diabetes. Diabetes Care 19:2012 (Published ahead of print November)

    Google Scholar 

  • Danne T, Mortensen HB, Hougaard P et al (2001) Persistent differences among centers over 3 years in glycemic control and hypoglycemia in a study of 3,805 children and adolescents with type 1 diabetes from the Hvidore Study Group. Diabetes Care 24:1342–1347

    PubMed  CAS  Google Scholar 

  • de Boer IH, Sun W, Cleary PA et al (2011) Intensive diabetes therapy and glomerular filtration rate in type 1 diabetes. N Engl J Med 365:2366–2376

    PubMed  Google Scholar 

  • Del Carro U, Fiorina P, Amadio S et al (2007) Evaluation of polyneuropathy markers in type 1 diabetic kidney transplant patients and effects of islet transplantation: neurophysiological and skin biopsy longitudinal analysis. Diabetes Care 30:3063–3069

    PubMed  Google Scholar 

  • DIAMOND Project Group (2006) Incidence and trends of childhood type 1 diabetes worldwide 1990–1999. Diabet Med 23:857–866

    Google Scholar 

  • Dor Y, Brown J, Martinez OI, Melton DA (2004) Adult pancreatic β-cells are formed by self-duplication rather than stem-cell differentiation. Nature 429:41–46

    PubMed  CAS  Google Scholar 

  • Egro FM (2013) Why is type 1 diabetes increasing? J Mol Endocrinol 51(1):R1–R13

    PubMed  CAS  Google Scholar 

  • Eich T, Eriksson O, Lundgren T (2007) Visualization of early engraftment in clinical islet transplantation by positron-emission tomography. N Engl J Med 356:2754–2755

    PubMed  CAS  Google Scholar 

  • English K (2012) Mechanisms of mesenchymal stromal cell immunomodulation. Immunol Cell Biol 91(1):19–26

    PubMed  Google Scholar 

  • Faradji RN, Tharavanij T, Messinger S et al (2008) Long-term insulin independence and improvement in insulin secretion after supplemental islet infusion under exenatide and etanercept. Transplantation 86:1658–1665

    PubMed  PubMed Central  Google Scholar 

  • Ferrannini E, Mari A, Nofrate V, Sosenko JM, Skyler JS (2010) Progression to diabetes in relatives of type 1 diabetic patients: mechanisms and mode of onset. Diabetes 59:679–685

    PubMed  CAS  PubMed Central  Google Scholar 

  • Figliuzzi M, Plati T, Cornolti R et al (2006) Biocompatibility and function of microencapsulated pancreatic islets. Acta Biomater 2:221–227

    PubMed  Google Scholar 

  • Fioretto P, Mauer SM, Bilous RW, Goetz FC, Sutherland DE, Steffes MW (1993) Effects of pancreas transplantation on glomerular structure in insulin-dependent diabetic patients with their own kidneys. Lancet 342:1193–1196

    PubMed  CAS  Google Scholar 

  • Fioretto P, Steffes MW, Sutherland DE, Goetz FC, Mauer M (1998) Reversal of lesions of diabetic nephropathy after pancreas transplantation. N Engl J Med 339:69–75

    PubMed  CAS  Google Scholar 

  • Fiorina P, Folli F, Zerbini G et al (2003) Islet transplantation is associated with improvement of renal function among uremic patients with type I diabetes mellitus and kidney transplants. J Am Soc Nephrol 14:2150–2158

    PubMed  Google Scholar 

  • Fiorina P, Gremizzi C, Maffi P et al (2005) Islet transplantation is associated with an improvement of cardiovascular function in type 1 diabetic kidney transplant patients. Diabetes Care 28:1358–1365

    PubMed  Google Scholar 

  • Fiorina P, Shapiro AM, Ricordi C, Secchi A (2008) The clinical impact of islet transplantation. Am J Transplant 8:1990–1997

    PubMed  CAS  Google Scholar 

  • Frank A, Deng S, Huang X et al (2004) Transplantation for type I diabetes: comparison of vascularized whole-organ pancreas with isolated pancreatic islets. Ann Surg 240:631–643

    PubMed  PubMed Central  Google Scholar 

  • Froud T, Ricordi C, Baidal DA et al (2005) Islet transplantation in type 1 diabetes mellitus using cultured islets and steroid-free immunosuppression: Miami experience. Am J Transplant 5:2037–2046

    PubMed  Google Scholar 

  • Froud T, Baidal DA, Faradji R et al (2008a) Islet transplantation with alemtuzumab induction and calcineurin-free maintenance immunosuppression results in improved short- and long-term outcomes. Transplantation 86:1695–1701

    PubMed  CAS  PubMed Central  Google Scholar 

  • Froud T, Faradji RN, Pileggi A et al (2008b) The use of exenatide in islet transplant recipients with chronic allograft dysfunction: safety, efficacy, and metabolic effects. Transplantation 86:36–45

    PubMed  PubMed Central  Google Scholar 

  • Gale EA (2005) Spring harvest? Reflections on the rise of type 1 diabetes. Diabetologia 48:2445–2450

    PubMed  CAS  Google Scholar 

  • Gangemi A, Salehi P, Hatipoglu B et al (2008) Islet transplantation for brittle type 1 diabetes: the UIC protocol. Am J Transplant 8:1250–1261

    PubMed  CAS  Google Scholar 

  • Garcea G, Weaver J, Phillips J et al (2009) Total pancreatectomy with and without islet cell transplantation for chronic pancreatitis: a series of 85 consecutive patients. Pancreas 38:1–7

    PubMed  Google Scholar 

  • Garcea G, Pollard CA, Illouz S, Webb M, Metcalfe MS, Dennison AR (2013) Patient satisfaction and cost-effectiveness following total pancreatectomy with islet cell transplantation for chronic pancreatitis. Pancreas 42:322–328

    PubMed  Google Scholar 

  • Gentilella R, Bianchi C, Rossi A, Rotella CM (2009) Exenatide: a review from pharmacology to clinical practice. Diabetes Obes Metab 11:544–556

    PubMed  CAS  Google Scholar 

  • Ghofaili KA, Fung M, Ao Z et al (2007) Effect of exenatide on β cell function after islet transplantation in type 1 diabetes. Transplantation 83:24–28

    PubMed  Google Scholar 

  • Gillard P, Ling Z, Mathieu C et al (2008) Comparison of sirolimus alone with sirolimus plus tacrolimus in type 1 diabetic recipients of cultured islet cell grafts. Transplantation 85:256–263

    PubMed  CAS  Google Scholar 

  • Goss JA, Goodpastor SE, Brunicardi FC et al (2004) Development of a human pancreatic islet-transplant program through a collaborative relationship with a remote islet-isolation center. Transplantation 77:462–466

    PubMed  Google Scholar 

  • Green A (2008) Descriptive epidemiology of type 1 diabetes in youth: incidence, mortality, prevalence, and secular trends. Endocr Res 33:1–15

    PubMed  Google Scholar 

  • Greenbaum CJ, Beam CA, Boulware D et al (2012) Fall in C-peptide during first 2 years from diagnosis: evidence of at least two distinct phases from composite type 1 diabetes trialNet data. Diabetes 61:2066–2073

    PubMed  CAS  PubMed Central  Google Scholar 

  • Groth C (2007) Towards developing guidelines on Xenotransplantation in China. Xenotransplantation 14:358–359

    Google Scholar 

  • Groth CG, Korsgren O, Tibell A et al (1994) Transplantation of porcine fetal pancreas to diabetic patients. Lancet 344:1402–1404

    PubMed  CAS  Google Scholar 

  • Gruessner AC, Sutherland DE (2005) 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 19:433–455

    PubMed  Google Scholar 

  • Gruessner RW, Sutherland DE, Gruessner AC (2005) Survival after pancreas transplantation. JAMA 293:675

    PubMed  CAS  Google Scholar 

  • Guignard AP, Oberholzer J, Benhamou PY et al (2004) Cost analysis of human islet transplantation for the treatment of type 1 diabetes in the Swiss-French Consortium GRAGIL. Diabetes Care 27:895–900

    PubMed  Google Scholar 

  • Hafiz MM, Faradji RN, Froud T et al (2005) Immunosuppression and procedure-related complications in 26 patients with type 1 diabetes mellitus receiving allogeneic islet cell transplantation. Transplantation 80:1718–1728

    PubMed  CAS  Google Scholar 

  • Hagopian W, Ferry RJ Jr, Sherry N et al (2013) Teplizumab preserves C-peptide in recent-onset type 1 diabetes: 2-year results from the randomized, placebo-controlled Protege trial. Diabetes 62(11):3901–3908

    PubMed  CAS  Google Scholar 

  • Halloran PF (2004) Immunosuppressive drugs for kidney transplantation. N Engl J Med 351:2715–2729

    PubMed  CAS  Google Scholar 

  • Harjutsalo V, Reunanen A, Tuomilehto J (2006) Differential transmission of type 1 diabetes from diabetic fathers and mothers to their offspring. Diabetes 55:1517–1524

    PubMed  CAS  Google Scholar 

  • Heneine W, Tibell A, Switzer WM et al (1998) No evidence of infection with porcine endogenous retrovirus in recipients of porcine islet-cell xenografts. Lancet 352:695–699

    PubMed  CAS  Google Scholar 

  • Hering BJ, Kandaswamy R, Harmon JV et al (2004) Transplantation of cultured islets from two-layer preserved pancreases in type 1 diabetes with anti-CD3 antibody. Am J Transplant 4:390–401

    PubMed  CAS  Google Scholar 

  • Hering BJ, Kandaswamy R, Ansite JD et al (2005) Single-donor, marginal-dose islet transplantation in patients with type 1 diabetes. JAMA 293:830–835

    PubMed  CAS  Google Scholar 

  • Hirshberg B (2006) Can we justify living donor islet transplantation? Curr Diab Rep 6:307–309

    PubMed  Google Scholar 

  • Hirshberg B, Rother KI, Digon BJ 3rd et al (2003) Benefits and risks of solitary islet transplantation for type 1 diabetes using steroid-sparing immunosuppression: the National Institutes of Health experience. Diabetes Care 26:3288–3295

    PubMed  Google Scholar 

  • Hu CY, Rodriguez-Pinto D, Du W et al (2007) Treatment with CD20-specific antibody prevents and reverses autoimmune diabetes in mice. J Clin Invest 117:3857–3867

    PubMed  CAS  PubMed Central  Google Scholar 

  • Huurman VA, Hilbrands R, Pinkse GG et al (2008) Cellular islet autoimmunity associates with clinical outcome of islet cell transplantation. PLoS One 3:e2435

    PubMed  PubMed Central  Google Scholar 

  • Huurman VA, Velthuis JH, Hilbrands R et al (2009) Allograft-specific cytokine profiles associate with clinical outcome after islet cell transplantation. Am J Transplant 9:382–388

    PubMed  CAS  Google Scholar 

  • Ichii H, Ricordi C (2009) Current status of islet cell transplantation. J Hepatobiliary Pancreat Surg 16:101–112

    PubMed  PubMed Central  Google Scholar 

  • Jin SM, Oh SH, Kim SK et al (2013) Diabetes-free survival in patients who underwent islet autotransplantation after 50 % to 60 % distal partial pancreatectomy for benign pancreatic tumors. Transplantation 95:1396–1403

    PubMed  Google Scholar 

  • Johansson H, Lukinius A, Moberg L et al (2005) Tissue factor produced by the endocrine cells of the islets of Langerhans is associated with a negative outcome of clinical islet transplantation. Diabetes 54:1755–1762

    PubMed  CAS  Google Scholar 

  • Keenan HA, Sun JK, Levine J et al (2010) Residual insulin production and pancreatic β-cell turnover after 50 years of diabetes: Joslin Medalist Study. Diabetes 59:2846–2853

    PubMed  CAS  PubMed Central  Google Scholar 

  • Kenmochi T, Asano T, Maruyama M et al (2009) Clinical islet transplantation in Japan. J Hepatobiliary Pancreat Surg 16:124–130

    PubMed  Google Scholar 

  • Keymeulen B, Vandemeulebroucke E, Ziegler AG et al (2005) Insulin needs after CD3-antibody therapy in new-onset type 1 diabetes. N Engl J Med 352:2598–2608

    PubMed  CAS  Google Scholar 

  • Keymeulen B, Gillard P, Mathieu C et al (2006) Correlation between β cell mass and glycemic control in type 1 diabetic recipients of islet cell graft. Proc Natl Acad Sci U S A 103:17444–17449

    PubMed  CAS  PubMed Central  Google Scholar 

  • Koh A, Senior P, Salam A et al (2010) Insulin-heparin infusions peritransplant substantially improve single-donor clinical islet transplant success. Transplantation 89:465–471

    PubMed  CAS  Google Scholar 

  • Kolb H, Elliott RB (1994) Increasing incidence of IDDM a consequence of improved hygiene? Diabetologia 37:729

    PubMed  CAS  Google Scholar 

  • Korsgren O, Nilsson B, Berne C et al (2005) Current status of clinical islet transplantation. Transplantation 79:1289–1293

    PubMed  Google Scholar 

  • Koulmanda M, Qipo A, Fan Z et al (2012) Prolonged survival of allogeneic islets in cynomolgus monkeys after short-term triple therapy. Am J Transplant 12:1296–1302

    PubMed  CAS  PubMed Central  Google Scholar 

  • Kyvik KO, Green A, Beck-Nielsen H (1995) Concordance rates of insulin dependent diabetes mellitus: a population based study of young Danish twins. BMJ 311:913–917

    PubMed  CAS  PubMed Central  Google Scholar 

  • Lachin JM, Genuth S, Nathan DM, Zinman B, Rutledge BN (2008) Effect of glycemic exposure on the risk of microvascular complications in the diabetes control and complications trial –revisited. Diabetes 57:995–1001

    PubMed  CAS  Google Scholar 

  • Lacy PE (1978) Workshop on Pancreatic Islet Cell Transplantation in Diabetes sponsored by the National Institute of Arthritis, Metabolism, and Digestive Diseases and held at the National Institutes of Health in Bethesda, Maryland, on November 29 and 30, 1977. Diabetes 27:427–429

    PubMed  CAS  Google Scholar 

  • Lee TC, Barshes NR, O’Mahony CA et al (2005) The effect of pancreatic islet transplantation on progression of diabetic retinopathy and neuropathy. Transplant Proc 37:2263–2265

    PubMed  CAS  Google Scholar 

  • Lee TC, Barshes NR, Agee EE, O’Mahoney CA, Brunicardi FC, Goss JA (2006) The effect of whole organ pancreas transplantation and PIT on diabetic complications. Curr Diab Rep 6:323–327

    PubMed  CAS  Google Scholar 

  • Leitao CB, Tharavanij T, Cure P et al (2008) Restoration of hypoglycemia awareness after islet transplantation. Diabetes Care 31:2113–2115

    PubMed  PubMed Central  Google Scholar 

  • Leitao CB, Cure P, Messinger S et al (2009) Stable renal function after islet transplantation: importance of patient selection and aggressive clinical management. Transplantation 87:681–688

    PubMed  PubMed Central  Google Scholar 

  • Lobo PI, Spencer C, Simmons WD et al (2005) Development of anti-human leukocyte antigen class 1 antibodies following allogeneic islet cell transplantation. Transplant Proc 37:3438–3440

    PubMed  CAS  Google Scholar 

  • Machen J, Harnaha J, Lakomy R, Styche A, Trucco M, Giannoukakis N (2004) Antisense oligonucleotides down-regulating costimulation confer diabetes-preventive properties to nonobese diabetic mouse dendritic cells. J Immunol 173:4331–4341

    PubMed  CAS  Google Scholar 

  • Maffi P, Bertuzzi F, De Taddeo F et al (2007) Kidney function after islet transplant alone in type 1 diabetes: impact of immunosuppressive therapy on progression of diabetic nephropathy. Diabetes Care 30:1150–1155

    PubMed  CAS  Google Scholar 

  • Maffi P, Balzano G, Ponzoni M et al (2013) Autologous pancreatic islet transplantation in human bone marrow. Diabetes 62(10):3523–3531

    PubMed  CAS  PubMed Central  Google Scholar 

  • Markmann JF, Rosen M, Siegelman ES et al (2003) Magnetic resonance-defined periportal steatosis following intraportal islet transplantation: a functional footprint of islet graft survival? Diabetes 52:1591–1594

    PubMed  CAS  Google Scholar 

  • Matsumoto S, Okitsu T, Iwanaga Y et al (2005) Insulin independence after living-donor distal pancreatectomy and islet allotransplantation. Lancet 365:1642–1644

    PubMed  CAS  Google Scholar 

  • Matsumoto S, Okitsu T, Iwanaga Y et al (2006) Follow-up study of the first successful living donor islet transplantation. Transplantation 82:1629–1633

    PubMed  Google Scholar 

  • Merani S, Toso C, Emamaullee J, Shapiro AM (2008) Optimal implantation site for pancreatic islet transplantation. Br J Surg 95:1449–1461

    PubMed  CAS  Google Scholar 

  • Mineo D, Sageshima J, Burke GW, Ricordi C (2009) Minimization and withdrawal of steroids in pancreas and islet transplantation. Transpl Int 22:20–37

    PubMed  Google Scholar 

  • Moran A, Bundy B, Becker DJ et al (2013) Interleukin-1 antagonism in type 1 diabetes of recent onset: two multicentre, randomised, double-blind, placebo-controlled trials. Lancet 381:1905–1915

    PubMed  CAS  Google Scholar 

  • Nagaya M, Katsuta H, Kaneto H, Bonner-Weir S, Weir GC (2009) Adult mouse intrahepatic biliary epithelial cells induced in vitro to become insulin-producing cells. J Endocrinol 201:37–47

    PubMed  CAS  Google Scholar 

  • Nathan DM, Cleary PA, Backlund JY et al (2005) Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes. N Engl J Med 353:2643–2653

    PubMed  Google Scholar 

  • Nathan DM, Zinman B, Cleary PA et al (2009) Modern-day clinical course of type 1 diabetes mellitus after 30 years’ duration: the diabetes control and complications trial/epidemiology of diabetes interventions and complications and Pittsburgh epidemiology of diabetes complications experience (1983–2005). Arch Intern Med 169:1307–1316

    PubMed  PubMed Central  Google Scholar 

  • Naziruddin B, Matsumoto S, Noguchi H et al (2012) Improved pancreatic islet isolation outcome in autologous transplantation for chronic pancreatitis. Cell Transplant 21:553–558

    PubMed  Google Scholar 

  • Nir T, Melton DA, Dor Y (2007) Recovery from diabetes in mice by β cell regeneration. J Clin Invest 117:2553–2561

    PubMed  CAS  PubMed Central  Google Scholar 

  • Nordwall M, Bojestig M, Arnqvist HJ, Ludvigsson J (2004) Declining incidence of severe retinopathy and persisting decrease of nephropathy in an unselected population of type 1 diabetes-the Linkoping Diabetes Complications Study. Diabetologia 47:1266–1272

    PubMed  CAS  Google Scholar 

  • O’Connell PJ, Hawthorne WJ, Holmes-Walker DJ et al (2006) Clinical islet transplantation in type 1 diabetes mellitus: results of Australia’s first trial. Med J Aust 184:221–225

    PubMed  Google Scholar 

  • Onkamo P, Vaananen S, Karvonen M, Tuomilehto J (1999) Worldwide increase in incidence of Type I diabetes – the analysis of the data on published incidence trends. Diabetologia 42:1395–1403

    PubMed  CAS  Google Scholar 

  • Orban T, Bundy B, Becker DJ et al (2011) Co-stimulation modulation with abatacept in patients with recent-onset type 1 diabetes: a randomised, double-blind, placebo-controlled trial. Lancet 378:412–419

    PubMed  CAS  PubMed Central  Google Scholar 

  • O’Sullivan ES, Vegas A, Anderson DG, Weir GC (2011) Islets transplanted in immunoisolation devices: a review of the progress and the challenges that remain. Endocr Rev 32:827–844

    PubMed  PubMed Central  Google Scholar 

  • Paty BW, Senior PA, Lakey JR, Shapiro AM, Ryan EA (2006) Assessment of glycemic control after islet transplantation using the continuous glucose monitor in insulin-independent versus insulin-requiring type 1 diabetes subjects. Diabetes Technol Ther 8:165–173

    PubMed  CAS  Google Scholar 

  • Peakman M (2013) Immunological pathways to β-cell damage in type 1 diabetes. Diabet Med 30:147–154

    PubMed  CAS  Google Scholar 

  • Pescovitz MD, Greenbaum CJ, Krause-Steinrauf H et al (2009) Rituximab, B-lymphocyte depletion, and preservation of β-cell function. N Engl J Med 361:2143–2152

    PubMed  CAS  Google Scholar 

  • Phillips B, Nylander K, Harnaha J et al (2008) A microsphere-based vaccine prevents and reverses new-onset autoimmune diabetes. Diabetes 57:1544–1555

    PubMed  CAS  PubMed Central  Google Scholar 

  • Porat S, Dor Y (2007) New sources of pancreatic β cells. Curr Diab Rep 7:304–308

    PubMed  CAS  Google Scholar 

  • Pugliese A (2013) The multiple origins of type 1 diabetes. Diabet Med 30:135–146

    PubMed  CAS  Google Scholar 

  • Rajotte RV (2008) Moving towards clinical application. Xenotransplantation 15:113–115

    PubMed  Google Scholar 

  • Redondo MJ, Rewers M, Yu L et al (1999) Genetic determination of islet cell autoimmunity in monozygotic twin, dizygotic twin, and non-twin siblings of patients with type 1 diabetes: prospective twin study. BMJ 318:698–702

    PubMed  CAS  PubMed Central  Google Scholar 

  • Rich SS (1990) Mapping genes in diabetes. Genetic epidemiological perspective. Diabetes 39:1315–1319

    PubMed  CAS  Google Scholar 

  • Rickels MR, Naji A (2009) Exenatide use in islet transplantation: words of caution. Transplantation 87:153

    PubMed  Google Scholar 

  • Rickels MR, Schutta MH, Mueller R et al (2005a) Islet cell hormonal responses to hypoglycemia after human islet transplantation for type 1 diabetes. Diabetes 54:3205–3211

    PubMed  CAS  Google Scholar 

  • Rickels MR, Schutta MH, Markmann JF, Barker CF, Naji A, Teff KL (2005b) β-Cell function following human islet transplantation for type 1 diabetes. Diabetes 54:100–106

    PubMed  CAS  Google Scholar 

  • Rickels MR, Schutta MH, Mueller R et al (2007) Glycemic thresholds for activation of counterregulatory hormone and symptom responses in islet transplant recipients. J Clin Endocrinol Metab 92:873–879

    PubMed  CAS  Google Scholar 

  • Rickels M, Cullison K, Fuller C (2011) Improvement of glucose counter-regulation following human islet transplantation in long-standing type 1 diabetes: preliminary results [abstract]. Diabetes 60:293, OR

    Google Scholar 

  • Robertson RP, Davis C, Larsen J, Stratta R, Sutherland DE (2006) Pancreas and islet transplantation in type 1 diabetes. Diabetes Care 29:935

    PubMed  Google Scholar 

  • Ruggenenti P, Remuzzi A, Remuzzi G (2008) Decision time for pancreatic islet-cell transplantation. Lancet 371:883–884

    PubMed  Google Scholar 

  • Russell SJ1, El-Khatib FH, Sinha M, Magyar KL, McKeon K, Goergen LG, Balliro C, Hillard MA, Nathan DM, Damiano ER (2014) Outpatient Glycemic Control with a Bionic Pancreas in Type 1 Diabetes. N Engl J Med. Jun 15. [Epub ahead of print]

    Google Scholar 

  • Ryan EA, Shandro T, Green K et al (2004a) Assessment of the severity of hypoglycemia and glycemic lability in type 1 diabetic subjects undergoing islet transplantation. Diabetes 53:955–962

    PubMed  CAS  Google Scholar 

  • Ryan EA, Paty BW, Senior PA, Shapiro AM (2004b) Risks and side effects of islet transplantation. Curr Diab Rep 4:304–309

    PubMed  Google Scholar 

  • Ryan EA, Paty BW, Senior PA et al (2005) Five-year follow-up after clinical islet transplantation. Diabetes 54:2060–2069

    PubMed  CAS  Google Scholar 

  • Ryan EA, Bigam D, Shapiro AM (2006) Current indications for pancreas or islet transplant. Diabetes Obes Metab 8:1–7

    PubMed  Google Scholar 

  • Schiopu A, Wood KJ (2008) Regulatory T cells: hypes and limitations. Curr Opin Organ Transplant 13:333–338

    PubMed  Google Scholar 

  • Secchi A, Socci C, Maffi P et al (1997) Islet transplantation in IDDM patients. Diabetologia 40:225–231

    PubMed  CAS  Google Scholar 

  • Senior PA, Zeman M, Paty BW, Ryan EA, Shapiro AM (2007) Changes in renal function after clinical islet transplantation: four-year observational study. Am J Transplant 7:91–98

    PubMed  CAS  Google Scholar 

  • Shapiro AM, Lakey JR, Ryan EA et al (2000) Islet transplantation in seven patients with type 1 diabetes mellitus using a glucocorticoid-free immunosuppressive regimen. N Engl J Med 343:230–238

    PubMed  CAS  Google Scholar 

  • Shapiro AM, Ricordi C, Hering BJ et al (2006) International trial of the Edmonton protocol for islet transplantation. N Engl J Med 355:1318–1330

    PubMed  CAS  Google Scholar 

  • Soltesz G, Patterson CC, Dahlquist G (2007) Worldwide childhood type 1 diabetes incidence – what can we learn from epidemiology? Pediatr Diabetes 8(Suppl 6):6–14

    PubMed  Google Scholar 

  • Sosenko JM, Palmer JP, Rafkin-Mervis L et al (2009) Incident dysglycemia and progression to type 1 diabetes among participants in the Diabetes Prevention Trial-Type 1. Diabetes Care 32:1603–1607

    PubMed  PubMed Central  Google Scholar 

  • Strachan DP (1989) Hay fever, hygiene, and household size. BMJ 299:1259–1260

    PubMed  CAS  PubMed Central  Google Scholar 

  • Sutherland DE (1981) Pancreas and islet transplantation. II. Clinical trials. Diabetologia 20:435–450

    PubMed  CAS  Google Scholar 

  • Sutherland DE, Matas AJ, Najarian JS (1978) Pancreatic islet cell transplantation. Surg Clin North Am 58:365–382

    PubMed  CAS  Google Scholar 

  • Sutherland DE, Gruessner AC, Carlson AM et al (2008) Islet autotransplant outcomes after total pancreatectomy: a contrast to islet allograft outcomes. Transplantation 86:1799–1802

    PubMed  Google Scholar 

  • Sykes M, Cozzi E, d’Apice A et al (2006) Clinical trial of islet xenotransplantation in Mexico. Xenotransplantation 13:371–372

    PubMed  Google Scholar 

  • Sykes M, Pierson RN 3rd, O’Connell P et al (2007) Reply to “critics slam Russian trial to test pig pancreas for diabetes”. Nat Med 13:662–663

    PubMed  CAS  Google Scholar 

  • Tateishi K, He J, Taranova O, Liang G, D’Alessio AC, Zhang Y (2008) Generation of insulin-secreting islet-like clusters from human skin fibroblasts. J Biol Chem 283:31601–31607

    PubMed  CAS  Google Scholar 

  • The Diabetes Control and Complications Trial Research Group (1993) The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med 329:977–986

    Google Scholar 

  • The Juvenile Diabetes Research Foundation Continuous Glucose Monitoring Study Group (2008) Continuous glucose monitoring and intensive treatment of type 1 diabetes. N Engl J Med 359:1464–1476

    Google Scholar 

  • Thompson DM, Begg IS, Harris C et al (2008) Reduced progression of diabetic retinopathy after islet cell transplantation compared with intensive medical therapy. Transplantation 85:1400–1405

    PubMed  Google Scholar 

  • Tuomilehto J, Podar T, Tuomilehto-Wolf E, Virtala E (1995) Evidence for importance of gender and birth cohort for risk of IDDM in offspring of IDDM parents. Diabetologia 38:975–982

    PubMed  CAS  Google Scholar 

  • Valdes-Gonzalez RA, Dorantes LM, Garibay GN et al (2005) Xenotransplantation of porcine neonatal islets of Langerhans and Sertoli cells: a 4-year study. Eur J Endocrinol 153:419–427

    PubMed  CAS  Google Scholar 

  • van der Windt DJ, Echeverri GJ, Ijzermans JN, Coopers DK (2008) The choice of anatomical site for islet transplantation. Cell Transplant 17:1005–1014

    PubMed  Google Scholar 

  • van der Windt DJ, Bottino R, Kumar G et al (2012) Clinical islet xenotransplantation: how close are we? Diabetes 61:3046–3055

    PubMed  PubMed Central  Google Scholar 

  • Venstrom JM, McBride MA, Rother KI, Hirshberg B, Orchard TJ, Harlan DM (2003) Survival after pancreas transplantation in patients with diabetes and preserved kidney function. JAMA 290:2817–2823

    PubMed  CAS  Google Scholar 

  • Venturini M, Fiorina P, Maffi P et al (2006) Early increase of retinal arterial and venous blood flow velocities at color Doppler imaging in brittle type 1 diabetes after islet transplant alone. Transplantation 81:1274–1277

    PubMed  Google Scholar 

  • Villiger P, Ryan EA, Owen R et al (2005) Prevention of bleeding after islet transplantation: lessons learned from a multivariate analysis of 132 cases at a single institution. Am J Transplant 5:2992–2998

    PubMed  CAS  Google Scholar 

  • Wahoff DC, Papalois BE, Najarian JS et al (1995) Autologous islet transplantation to prevent diabetes after pancreatic resection. Ann Surg 222:562–575 (discussion 575–569, 1995)

    PubMed  CAS  PubMed Central  Google Scholar 

  • Wang W (2007) A pilot trial with pig-to-man islet transplantation at the 3rd Xiang-Ya Hospital of the Central South University in Changsha. Xenotransplantation 14:358

    Google Scholar 

  • Warnock GL, Meloche RM, Thompson D et al (2005) Improved human pancreatic islet isolation for a prospective cohort study of islet transplantation vs best medical therapy in type 1 diabetes mellitus. Arch Surg 140:735–744

    PubMed  Google Scholar 

  • Warnock GL, Thompson DM, Meloche RM et al (2008) A multi-year analysis of islet transplantation compared with intensive medical therapy on progression of complications in type 1 diabetes. Transplantation 86:1762–1766

    PubMed  Google Scholar 

  • Weaver TA, Kirk AD (2007) Alemtuzumab. Transplantation 84:1545–1547

    PubMed  CAS  Google Scholar 

  • White SA, Shaw JA, Sutherland DE (2009) Pancreas transplantation. Lancet 373:1808–1817

    PubMed  CAS  Google Scholar 

  • Yeh HC1, Brown TT, Maruthur N, Ranasinghe P, Berger Z, Suh YD, Wilson LM, Haberl EB, Brick J, Bass EB, Golden SH (2012) Comparative effectiveness and safety of methods of insulin delivery and glucose monitoring for diabetes mellitus: a systematic review and meta-analysis. Ann Intern Med. Sep 4;157(5):336–47

    Google Scholar 

  • Zhou Q, Brown J, Kanarek A, Rajagopal J, Melton DA (2008) In vivo reprogramming of adult pancreatic exocrine cells to β-cells. Nature 455:627–632

    PubMed  CAS  Google Scholar 

  • Ziegler AG, Rewers M, Simell O et al (2013) Seroconversion to multiple islet autoantibodies and risk of progression to diabetes in children. JAMA 309:2473–2479

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Paolo Cravedi .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer Science+Business Media Dordrecht

About this entry

Cite this entry

Cravedi, P., Ruggenenti, P., Remuzzi, G. (2015). Successes and Disappointments with Clinical Islet Transplantation. In: Islam, M. (eds) Islets of Langerhans. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-6686-0_23

Download citation

Publish with us

Policies and ethics