Abstract
For a subset of patients with complicated Type I Diabetes Mellitus (T1DM), islet transplantation has become a well-established treatment modality. Before 2000, fewer than 9% of islet transplant recipient maintained insulin independence for greater than one year. The improvements resulting from the Edmonton Protocol have led to high rates of one-year insulin independence, and together with an international collaboration, propagated the expansion of clinical islet transplantation centers worldwide. In spite of the continued success of clinical islet transplantation, a number of limitations with this therapy remain, including the requirement for lifelong immunosuppression with the associated side effects. While islet transplantation is currently generally reserved for adults with T1DM with severe hypoglycemia or glycemic lability, we herein consider the possibility of its application to the pediatric population, moving this therapy one day from a treatment for some to a potential cure for all.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
King H, Aubert RE, Herman WH. Global burden of diabetes, 1995–2025: prevalence, numerical estimates, and projections. Diabetes Care. 1998;21(9):1414–31.
Polonsky KS. The past 200 years in diabetes. New Engl J Med. 2012;367(14):1332–40.
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):141–6.
The Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. New Engl J Med. 1993;329(14):977–86.
Keen H. The diabetes control and complications trial (DCCT). Health Trends. 1994;26(2):41–3.
Nathan DM, Lachin J, Cleary P, Orchard T, Brillon DJ, Backlund JY, et al. Intensive diabetes therapy and carotid intima-media thickness in type 1 diabetes mellitus. New Engl J Med. 2003;348(23):2294–303.
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):827–37.
Brogard JM, Vetter T, Blickle JF. Discovery of pancreatic diabetes in Strasbourg. Diabete Metabol. 1992;18(2):104–14.
Agarwal A, Brayman KL. Update on islet cell transplantation for type 1 diabetes. Semin Intervent Radiol. 2012;29(2):90–8.
Lacy PE, Kostianovsky M. Method for the isolation of intact islets of Langerhans from the rat pancreas. Diabetes. 1967;16(1):35–9.
Misler S. The isolated pancreatic islet as a micro-organ and its transplantation to cure diabetes: celebrating the legacy of Paul Lacy. Islets. 2010;2(4):210–24.
Reckard CR, Ziegler MM, Barker CF. Physiological and immunological consequences of transplanting isolated pancreatic islets. Surgery. 1973;74(1):91–9.
Shapiro AM. A historical perspective on experimental and clinical islet transplantation. Informa Health Care. 2007;1.
Lakey JR, Warnock GL, Shapiro AM, Korbutt GS, Ao Z, Kneteman NM, et al. Intraductal collagenase delivery into the human pancreas using syringe loading or controlled perfusion. Cell Transplant. 1999;8(3):285–92.
Ricordi C, Lacy PE, Scharp DW. Automated islet isolation from human pancreas. Diabetes. 1989;38(Suppl 1):140–2.
Shapiro AM, Lakey JR, Ryan EA, Korbutt GS, Toth E, Warnock GL, et al. Islet transplantation in seven patients with type 1 diabetes mellitus using a glucocorticoid-free immunosuppressive regimen. New Engl J Med. 2000;343(4):230–8.
Ryan EA, Bigam D, Shapiro AM. Current indications for pancreas or islet transplant. Diabetes Obes Metab. 2006;8(1):1–7.
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):686–9.
Najarian JS, Sutherland DE, Matas AJ, Steffes MW, Simmons RL, Goetz FC. Human islet transplantation: a preliminary report. Transpl Proc. 1977;9(1):233–6.
Brendel M HB, Shulz A, Bretzel R. International islet transplant registry report. 1999.1–20.
Benhamou PY, Watt PC, Mullen Y, Ingles S, Watanabe Y, Nomura Y, et al. Human islet isolation in 104 consecutive cases. Factors affecting isolation success. Transplantation. 1994;57(12):1804–10.
Goto M, Eich TM, Felldin M, Foss A, Kallen R, Salmela K, 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):1367–75.
Ihm SH, Matsumoto I, Sawada T, Nakano M, Zhang HJ, Ansite JD, et al. Effect of donor age on function of isolated human islets. Diabetes. 2006;55(5):1361–8.
Lakey JR, Rajotte RV, Warnock GL, Kneteman NM. Human pancreas preservation prior to islet isolation. Cold ischemic tolerance. Transplantation. 1995;59(5):689–94.
Lakey JR, Warnock GL, Rajotte RV, Suarez-Alamazor ME, Ao Z, Shapiro AM, et al. Variables in organ donors that affect the recovery of human islets of Langerhans. Transplantation. 1996;61(7):1047–53.
Matsumoto I, Sawada T, Nakano M, Sakai T, Liu B, Ansite JD, et al. Improvement in islet yield from obese donors for human islet transplants. Transplantation. 2004;78(6):880–5.
Nano R, Clissi B, Melzi R, Calori G, Maffi P, Antonioli B, et al. Islet isolation for allotransplantation: variables associated with successful islet yield and graft function. Diabetologia. 2005;48(5):906–12.
Zeng Y, Torre MA, Karrison T, Thistlethwaite JR. The correlation between donor characteristics and the success of human islet isolation. Transplantation. 1994;57(6):954–8.
Kin T, Murdoch TB, Shapiro AM, Lakey JR. Estimation of pancreas weight from donor variables. Cell Transplant. 2006;15(2):181–5.
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 2):23–6.
Berney T, Johnson PR. Donor pancreata: evolving approaches to organ allocation for whole pancreas versus islet transplantation. Transplantation. 2010;90(3):238–43.
O’Gorman D, Kin T, Murdoch T, Richer B, McGhee-Wilson D, Ryan E, et al. The standardization of pancreatic donors for islet isolation. Transpl Proc. 2005;37(2):1309–10.
de Boer J, De Meester J, Smits JM, Groenewoud AF, Bok A, van der Velde O, et al. Eurotransplant randomized multicenter kidney graft preservation study comparing HTK with UW and Euro-Collins. Transpl Int. 1999;12(6):447–53.
Hering BJ, Matsumoto I, Sawada T, Nakano M, Sakai T, Kandaswamy R, et al. Impact of two-layer pancreas preservation on islet isolation and transplantation. Transplantation. 2002;74(12):1813–6.
Benhamou PY, Oberholzer J, Toso C, Kessler L, Penfornis A, Bayle F, et al. 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. 2001;44(7):859–64.
Goss JA, Schock AP, Brunicardi FC, Goodpastor SE, Garber AJ, Soltes G, et al. Achievement of insulin independence in three consecutive type-1 diabetic patients via pancreatic islet transplantation using islets isolated at a remote islet isolation center. Transplantation. 2002;74(12):1761–6.
Wolters GH, Vos-Scheperkeuter GH, van Deijnen JH, van Schilfgaarde R. An analysis of the role of collagenase and protease in the enzymatic dissociation of the rat pancreas for islet isolation. Diabetologia. 1992;35(8):735–42.
Johnson PR, White SA, London NJ. Collagenase and human islet isolation. Cell Transplant. 1966;15(4):437–52.
Wang X, Meloche M, Verchere CB, Ou D, Mui A, Warnock GL. Improving islet engraftment by gene therapy. J Transplant. 2011;2011:594851.
Mehigan DG, Bell WR, Zuidema GD, Eggleston JC, Cameron JL. Disseminated intravascular coagulation and portal hypertension following pancreatic islet autotransplantation. Ann Surg. 1980;191(3):287–93.
Lake SP, Bassett PD, Larkins A, Revell J, Walczak K, Chamberlain J, et al. Large-scale purification of human islets utilizing discontinuous albumin gradient on IBM 2991 cell separator. Diabetes. 1989;38(Suppl 1):143–5.
Ichii HPA, Khan A, Fraker C, Ricordi C. Culture and transportation of human islets between centers. Islet transplantation and beta cell replacement therapy. New York: Informa healthcare; 2007. p. 251.
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(7):830–5.
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(6):1250–61.
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(8):2037–46.
Froud T, Faradji RN, Pileggi A, Messinger S, Baidal DA, Ponte GM, et al. The use of exenatide in islet transplant recipients with chronic allograft dysfunction: safety, efficacy, and metabolic effects. Transplantation. 2008;86(1):36–45.
Ghofaili KA, Fung M, Ao Z, Meloche M, Shapiro RJ, Warnock GL, et al. Effect of exenatide on beta cell function after islet transplantation in type 1 diabetes. Transplantation. 2007;83(1):24–8.
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(12):1658–65.
Rajab A. Islet transplantation: alternative sites. Curr Diab Rep. 2010;10(5):332–7.
Froud T, Yrizarry JM, Alejandro R, Ricordi C. Use of D-STAT to prevent bleeding following percutaneous transhepatic intraportal islet transplantation. Cell Transplant. 2004;13(1):55–9.
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(3):353–61.
Biarnes M, Montolio M, Nacher V, Raurell M, Soler J, Montanya E. Beta-cell death and mass in syngeneically transplanted islets exposed to short- and long-term hyperglycemia. Diabetes. 2002;51(1):66–72.
Owen RJ, Ryan EA, O’Kelly K, Lakey JR, McCarthy MC, Paty BW, et al. Percutaneous transhepatic pancreatic islet cell transplantation in type 1 diabetes mellitus: radiologic aspects. Radiology. 2003;229(1):165–70.
Ryan EA, Paty BW, Senior PA, Bigam D, Alfadhli E, Kneteman NM, et al. Five-year follow-up after clinical islet transplantation. Diabetes. 2005;54(7):2060–9.
Gala-Lopez B, Pepper AR, Shapiro AM. Biologic agents in islet transplantation. Curr Diab Rep. 2013;13(5):713–22.
Bloom SR, Polak JM. Somatostatin. Br Med J. 1987;295(6593):288–90.
Korsgren O, Lundgren T, Felldin M, Foss A, Isaksson B, Permert J, et al. Optimising islet engraftment is critical for successful clinical islet transplantation. Diabetologia. 2008;51(2):227–32.
Shapiro AM. A historical perspective on experimental and clinical islet transplantation. In: Shapiro AM, Shaw JA, editors. Islet transplantation and beta cell replacement therapy. New York, London: Informa Healthcare; 2007.
Gabardi S, Martin ST, Roberts KL, Grafals M. Induction immunosuppressive therapies in renal transplantation. Am J Health-System Pharm: AJHP: Official J Am Soc Health-System Pharmacists. 2011;68(3):211–8.
Hering BJ. Repurification: rescue rather than routine remedy. Am J Transplant. 2005;5(1):1–2.
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):465–71.
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-1-beta and TNF-alpha. Cell Transplant. 2011;20(10):1641–7.
Shapiro AM, Ricordi C. Unraveling the secrets of single donor success in islet transplantation. Am J Transplant. 2004;4(3):295–8.
Xenos ES, Farney AC, Widmer MB, Casanova D, Stevens RB, Blazar BR, et al. Effect of tumor necrosis factor alpha and of the soluble tumor necrosis factor receptor on insulin secretion of isolated islets of Langerhans. Transpl Proc. 1992;24(6):2863–4.
Senior PA, Paty BW, Cockfield SM, Ryan EA, Shapiro AM. Proteinuria developing after clinical islet transplantation resolves with sirolimus withdrawal and increased tacrolimus dosing. Am J Transplant. 2005;5(9):2318–23.
Kaplan B, Schold J, Srinivas T, Womer K, Foley DP, Patton P, et al. Effect of sirolimus withdrawal in patients with deteriorating renal function. Am J Transplant. 2004;4(10):1709–12.
The CITR Coordinating Center and Investigators. The collaborative islet transplant registry (CITR) 2011 seventh annual report. https://web.emmes.com/study/isl/reports/01062012_7thAnnualReport.pdf. Accessed 27 Jan 2017.
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(7):1436–45.
Senior PA, Kin T, Shapiro AMJ, Koh A. Islet transplantation at the University of Alberta: status update and review of progress over the last decade. Can J Diabetes. 2012;36:32–7.
Pepper AR, Gala-Lopez B, Ziff O, Shapiro AJ. Current status of clinical islet transplantation. World J Transplant. 2013;3(4):48–53.
Senior PAKT, Shapiro AMJ, Koh A. Islet transplantation at the University of Alberta: Status update and review of progress over the last decade. Can J Diabetes. 2012;36:32–7.
Ly TT, Nicholas JA, Retterath A, Lim EM, Davis EA, Jones TW. 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(12):1240–7.
Shapiro AM. Strategies toward single-donor islets of Langerhans transplantation. Curr Opin Organ Transplant. 2011;16(6):627–31.
Thompson DM, Meloche M, Ao Z, Paty B, Keown P, Shapiro RJ, et al. Reduced progression of diabetic microvascular complications with islet cell transplantation compared with intensive medical therapy. Transplantation. 2011;91(3):373–8.
Ryan EA, Shandro T, Green K, Paty BW, Senior PA, Bigam D, et al. Assessment of the severity of hypoglycemia and glycemic lability in type 1 diabetic subjects undergoing islet transplantation. Diabetes. 2004;53(4):955–62.
Patrick AW, Campbell IW. Fatal hypoglycaemia in insulin-treated diabetes mellitus: clinical features and neuropathological changes. Diabet Med. 1990;7(4):349–54.
Gonder-Frederick LA, Clarke WL, Cox DJ. The Emotional, Social, and Behavioral Implications of Insulin-Induced Hypoglycemia. Semin Clin Neuropsychiatry. 1997;2(1):57–65.
Hathout E, Lakey J, Shapiro J. Islet transplant: an option for childhood diabetes? Arch Dis Child. 2003;88(7):591–4.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2018 Springer-Verlag GmbH Germany
About this chapter
Cite this chapter
Bruni, A., McCall, M., James Shapiro, A.M. (2018). Islet Cell Transplantation. In: Ledbetter, D., Johnson, P. (eds) Endocrine Surgery in Children. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-54256-9_14
Download citation
DOI: https://doi.org/10.1007/978-3-662-54256-9_14
Published:
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-662-54254-5
Online ISBN: 978-3-662-54256-9
eBook Packages: MedicineMedicine (R0)