Current status of clinical islet transplantation: Advances and obstacles

Current Opinion in Endocrinology and Diabetes

Volumn 11, Issue 2, 2004, Pages 98-103

  Wiseman, Alexander C ^a   Gill, Ronald G ^b  

^a UNIVERSITY OF COLORADO   (United States)

^b UNIVERSITY OF COLORADO DENVER   (United States)

Author keywords

Euglycemia; Islet transplantation; Type 1 diabetes

Indexed keywords

CLINICAL PROTOCOL; HUMAN; INSULIN DEPENDENT DIABETES MELLITUS; METHODOLOGY; NONHUMAN; PANCREAS ISLET TRANSPLANTATION; REPLICATION STUDY; REVIEW; TREATMENT OUTCOME;

EID: 22344432458     PISSN: 10683097     EISSN: None     Source Type: Journal    
DOI: 10.1097/01.med.0000129642.42263.66     Document Type: Review

References (46)

1. Hering BJ: International islet transplant registry. Minneapolis: University of Minnesota; 1999.
2. Shapiro AMJ, Lakey JRT, Ryan EA, et al.: Islet transplantation in seven patients with type I diabetes mellitus using a glucocorticoid-free immunosupressive regimen. N Engl J Med 2000, 343:230-238. This landmark trial indicated for the first time that reproducible insulin independence could be achieved in Type 1 diabetic recipients using solitary islet allografts.
3. Shapiro AM, Ricordi C, Hering BJ: Edmonton's islet success has indeed been replicated elsewhere. Lancet 2003, 386:1242. Although only a preliminary report, this brief communication indicates that the success of the Edmonton protocol has been reproduced by other islet transplant centers.
4. Markmann JF, Deng S, Huang X, et al.: Insulin independence following isolated islet transplantation and single islet infusions. Ann Surg 2003, 237:741-750. To date this is the most robust published report of replicating the initial Edmonton results. Also, this group shows a high frequency of achieving insulin independence with single islet donor infusions.
5. Goss JA, Schock AP, Brunicardi FC, 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, 74:1761-1766. This study is important because it demonstrates that another center can replicate the initial Edmonton results and also demonstrates that geographically distant centers can collaborate for successful islet transplants.
6. Kaufman DB, Baker MS, Chen X, et al.: Sequential kidney/islet transplantation using prednisone-free immunosuppression. Am J Transplant 2002, 2:674-677.
7. Hirshberg B, Rother KI, Digon BJI, et al.: Benefits and risks of solitary islet transplanation for Type 1 Diabetes using steroid-sparing immunosuppression. Diabetes Care 2003, 26:3288-3295. This is an important result for two reasons: Firstly, this is another group that has replicated the Edmonton success. However, this study also reports increased patient dissatisfaction with solitary islet transplantation despite graft function relative to previous results. As such, this study illustrates the importance of determining the 'cost/benefit' of islet transplantation in pre-uremic diabetic patients.
8. Robertson RP: Islet transplantation as a treatment for diabetes-a work in progress. N Engl J Med 2004, 350:694-705.
9. Ryan EA, Lakey JRT, Paty BW, et al.: Successful islet transplantation: continued insulin reserve provides long-term glycemic control. Diabetes 2002, 51:2148-2157. Very important report with the most recent follow-up results of solitary islet allograft survival and function from the 'Edmonton' protocol.
10. Robertson RP, Davis C, Larsen J, et al.: Pancreas and islet transplantation for patients with diabetes. Diabetes Care 2000, 23:112-116.
11. Hering BJ, Kandaswamy R, Harmon JV, et al.: Transplantation of cultured islets from two-layer preserved pancreases in Type 1 diabetes with anti-CD3 antibody. Am J Transplant 2004, 4:390-401. A very important study for two reasons: This trial represents a major deviation from the original Edmonton protocol for solitary islet transplantation by using a modified, non-mitogenic humanized anti-CD3 monoclonal antibody as a primary induction agent. Also, this study has a very high rate of insulin independence using single islet donor infusions.
12. Herold KC, Hagopian W, Auger JA, et al.: Anti-CD3 monoclonal antibody in new-onset type 1 diabetes mellitus. N Engl J Med 2002, 346:1692-1698.
13. Meyer C, Hering BJ, Grossmann R, et al.: Improved glucose counterregulation and autonomic symptoms after intraportal islet transplants alone in patients with long-standing type I diabetes mellitus. Transplantation 1998, 66:233-240.
14. Luzi L, Perseghin G, Brendel MD, et al.: Metabolic effects of restoring partial β-cell function after islet allotransplantation in Type 1 diabetic patients. Diabetes 2001, 50:277-282.
15. 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. An interesting attempt to develop an algorithm for providing a quantitative measure of a glucose lability 'index' in islet transplant recipients.
16. Paty BW, Ryan EA, Shapiro AM, et al.: Intrahepatic islet transplantation in type 1 diabetic patients does not restore hypoglycemic hormonal counterregulation or symptom recognition after insulin independence. Diabetes 2002, 51:3428-3434. This study introduces an important caveat to current islet transplantation by showing that counterregulation in the form of a glucagon response to hypoglycemia is not restored by intrahepatic islet allografts using the 'Edmonton' protocol.
17. Fioretto PF, Steffes MW, Sutherland DER, et al.: Reversal of lesions of diabetic neuropathy after pancreas transplantation. N Engl J Med 1998, 339:69-75.
18. Fiorina P, Folli F, Maffi P, et al.: Islet transplantation improves vascular diabetic complications in patients with diabetes who underwent kidney transplantation: a comparison between kidney-pancreas and kidney-alone transplantation. Transplantation 2003, 75:1296-1301. Important recent study supporting the concept that islet transplants can impact the progression of diabetes-related complications.
19. Ricordi C: Lilly lecture 2002. Islet transplantation: a brave new world. Diabetes 2003, 52:199-203.
20. Ricordi C, Strom TB: Clinical islet transplantation: advances and immunological challenges. Nat Rev Immunol 2004, 4:259-268. An outstanding recent review of the history and status of clinical islet transplantation combined with a discussion of important future prospects for immunological tolerance induction.
21. Balamurugan AN, Chang Y, Fung JJ, et al.: Flexible management of enzymatic digestion improves human islet isolation outcome from sub-optimal donor pancreata. Am J Transplant 2003, 3:1135-1142.
22. Johnson PR, White SA, London NJ: Collagenase and human islet isolation. Cell Transplant 1996, 5:437-452.
23. Brandhorst H, Brandhorst D, Hesse F, et al.: Successful human islet isolation utilizing recombinant collagenase. Diabetes 2003, 52:1143-1146. A proof-of-concept study indicating that a defined, recombinant collagenase reagent can potentially substitute for currently used products purified from crude enzyme preparations for human islet isolation. This result could potentially provide a very significant advance in the standardization of islet isolation.
24. Lakey JR, Warnock GL, Rajotte RV, et al.: Variables in organ donors that affect the recovery of human islets of Langerhans. Transplantation 1996, 61:1047-1053.
25. Lakey JR, Kneteman NM, Rajotte RV, et al.: Effect of core pancreas temperature during cadaveric procurement on human islet isolation and functional viability. Transplantation 2002, 73:1106-1110.
26. Lakey JR, Rajotte RV, Warnock GL, Kneteman NM: Human pancreas preservation prior to islet isolation. Cold ischemic tolerance. Transplantation 1995, 59:689-694.
27. Markmann JF, Deng S, Desai NM, et al.: The use of non-heart-beating donors for isolated pancreatic islet transplantation. Transplantation 2003, 75:1423-1429. Potentially very important result that could lead to an expansion of the donor pancreas pool for human islet isolation.
28. Hering B, Matsumoto I, Sawada T, et al.: Impact of two-layer pancreas preservation on islet isolation and transplantation. Transplantation 2002, 74:1813-1816.
29. Ricordi C, Fraker C, Szust J, et al.: Improved human islet isolation outcome from marginal donors following addition of oxygenated perfluorocarbon to cold-storage solution. Transplantation 2003, 75:1524-1527.
30. Tsujimura T, Kuroda Y, Churchill TA, et al.: Short-term storage of the ischemically damage human pancreas by the two-layer method prior to islet isolation. Cell Transplant 2004, 13:67-73. References 29 and 30 illustrate the advantage of the '2-layer' method of pancreas preservation for capturing suboptimal donors for islet isolation.
31. Thomas D, Yang H, Boffa DJ, et al.: Proapoptotic bax is hyperexpressed in isolated human islets compared with antiapoptotic bcl-2. Transplantation 2002, 74:1489-1496.
32. Johansson U, Olsson A, Gabrielsson S, et al.: Inflammatory mediators expressed in himan islets of Langerhans: implications for islet transplantation. Biochem Biophys Res Comm 2003, 308:474-479.
33. Bottino R, Balamurugan AN, Bertera S, et al.: Preservation of human islet cell functional mass by anti-oxidative action of a novel SOD mimic compound. Diabetes 2002, 51:2561-2567.
34. Farilla L, Bulotta A, Hirshberg B, et al.: Glucagon-like peptide 1 inhibits cell apoptosis and improves glucose responsiveness of freshly isolated human islets. Endocrinology 2003, 144:5149-5158.
35. Giannoukakis N, Mi Z, Rudert WA, et al.: Prevention of beta cell dysfunction and apoptosis activation in human islets by adenoviral gene transfer of the insulin-like growth factor I. Gene Ther 2000, 7:2015-2022.
36. Rabinovitch A, Suarez-Pinzon W, Strynadka K, et al.: Transfection of human pancreatic islets with an anti-apoptotic gene (bcl-2) protects β-cells from cytokine-induced destruction. Diabetes 1999, 48:1223-1229.
37. Bennet W, Sundberg B, Groth CG, et al.: Incompatibility between human blood and isolated islets of Langerhans: a finding with implications for clinical intraportal islet transplantation? Diabetes 1999, 48:1907-1914.
38. 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, 360:2039-2045. A finding with potentially great impact on human islet transplantation. This study shows that tissue factor expression by isolated islet cells can trigger a thrombotic reaction that may account for at least some islet failure seen in clinical transplants.
39. Ozmen L, Ekdahl KN, Elgue G, et al.: Inhibition of thrombin abrogates the instant blood-mediated inflammatory reaction triggered by isolated human islets: possible application of the thrombin inhibitor melagatran in clinical islet transplantation. Diabetes 2002, 51:1779-1784.
40. Moberg L, Olsson A, Berne C, et al.: Nicotinamide inhibits tissue factor expression in isolated human pancreatic islets: implications for clinical islet transplantation. Transplantation 2003, 76:1285-1288.
41. Sutherland DER, Sibley R, Xu XZ, et al.: Twin-to-twin pancreas transplantation: Reversal and reenactment of the pathogenesis of type I diabetes. Transplant Assoc Am Physicians 1984, 97:80-87.
42. Wahoff DC, Papalois BE, Najarian JS, et al.: Autologous islet transplantation to prevent diabetes after pancreatic resection. Ann Surg 1995, 222:562-579.
43. Roep BO, Stobbe I, Duinkerken G, et al.: Auto- and alloimmune reactivity to human islet allografts transplanted into Type 1 diabetic patients. Diabetes 1999, 48:484-490.
44. Stegall MD, Lafferty KJ, Kam I, Gill RG: Evidence of recurrent autoimmunity in human allogeneic islet transplantation. Transplantation 1996, 61:1272-1274.
45. Adams AB, Shirasugi N, Durham MM, et al.: Calcineurin inhibitor-free CD28 blockade-based protocol protects allogeneic islets in nonhuman primates. Diabetes 2002, 51:265-270. Very important application of a recently generated reagent (LEA29Y) that has high affinity for costimulatory molecules involved in T lymphocyte activation. Importantly, this reagent was effective in preventing islet allograft rejection in a large-animal, non-human primate model.
46. Zheng XX, Sanchez-Fueyo A, Sho M, et al.: Favorably tipping the balance between cytopathic and regulatory T cells to create transplantation tolerance. Immunity 2003, 19:503-514. This approach (also described in reference 20) is a rare example of an intervention successful for achieving long-term islet allograft survival in the very stringent diabetic NOD mouse model of autoimmune diabetes.