Advertisement

Current Diabetes Reports

, Volume 10, Issue 5, pp 332–337 | Cite as

Islet Transplantation: Alternative Sites

  • Amer Rajab
Article

Abstract

The portal vein is currently the site of choice for clinical islet transplantation, even though it is far from being an ideal site. Low oxygen tension and the induction of an inflammatory response impair islet implantation and lead to significant early loss. Even if enough islets survive the early implantation period to render insulin independence, few patients maintain it. Therefore, the search for an ideal site for islet transplantation continues. Experimentally, islets have been transplanted into the portal vein, kidney subcapsule, spleen, pancreas, peritoneum, omentum, gastrointestinal wall, testis, thymus, bone marrow, anterior chamber of the eye, cerebral ventricles, and subcutaneous and intramuscular spaces. Some of these sites are suitable for gathering scientific data, whereas others have potential clinical application. Varying degrees of success have been reported with the use of all these transplant sites in an experimental setting. However, the optimal transplant site remains to be finally established.

Keywords

Islet transplantation Sites Liver Kidney subcapsule Spleen Pancreas Peritoneum Gastrointestinal walls Bone marrow Subcutaneous 

Notes

Disclosure

No potential conflict of interest relevant to this article was reported.

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Ballian N, Brunicardi FC: Islet vasculature as a regulator of endocrine pancreas function. World J Surg 2007, 31:705–714.CrossRefPubMedGoogle Scholar
  2. 2.
    Ryan EA, Lakey JR, Paty BW, et al.: Successful islet transplantation: continued insulin reserve provides long-term glycemic control. Diabetes 2002, 51:2148–2157.CrossRefPubMedGoogle Scholar
  3. 3.
    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.CrossRefPubMedGoogle Scholar
  4. 4.
    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, 54:1755–1762.CrossRefPubMedGoogle Scholar
  5. 5.
    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.CrossRefPubMedGoogle Scholar
  6. 6.
    Berman DM, Cabrera O, Kenyon NM, et al.: Interference with tissue factor prolongs intrahepatic islet allograft survival in a nonhuman primate marginal mass model. Transplantation 2007, 84:308–315.CrossRefPubMedGoogle Scholar
  7. 7.
    Bottino R, Fernandez LA, Ricordi C, et al.: Transplantation of allogeneic islets of Langerhans in the rat liver: Effects of macrophage depletion on graft survival and microenvironment activation. Diabetes 1998, 47:316–323.CrossRefPubMedGoogle Scholar
  8. 8.
    Barshes NR, Wyllie S, Goss JA: Inflammation-mediated dysfunction and apoptosis in pancreatic islet transplantation: implications for intrahepatic grafts. J Leukoc Biol 2005, 77:587–597.CrossRefPubMedGoogle Scholar
  9. 9.
    Desai NM, Goss JA, Deng S, et al.: Elevated portal vein drug levels of sirolimus and tacrolimus in islet transplant recipients: local immunosuppression or islet toxicity? Transplantation 2003, 76:1623–1625.CrossRefPubMedGoogle Scholar
  10. 10.
    •• Lau J, Mattsson G, Carlsson C, et al.: Implantation site-dependent dysfunction of transplanted pancreatic islets. Diabetes 2007, 56:1544–1550. This article describes the influence of the implantation microenvironment on islet function.CrossRefPubMedGoogle Scholar
  11. 11.
    Alejandro R, Cutfield RG, Shienvold FL, et al.: Natural history of intrahepatic canine islet cell autografts. J Clin Invest 1986, 78:1339–1348.CrossRefPubMedGoogle Scholar
  12. 12.
    Kim HI, Yu JE, Park CG, Kim SJ: Comparison of four pancreatic islet implantation sites. J Korean Med Sci 2010, 25:203–210.CrossRefPubMedGoogle Scholar
  13. 13.
    Reece-Smith H, DuToiit DF, McShane P, Morris PJ: Prolonged survival of pancreatic islet allografts transplanted beneath the renal capsule. Transplantation 1981, 31:305–306.CrossRefPubMedGoogle Scholar
  14. 14.
    Lake SP, Chamberlain J, Husken P, et al.: In vivo assessment of isolated pancreatic islet viability using the streptozotocin-induced diabetic nude rat. Diabetologia 1988, 31:390–394.CrossRefPubMedGoogle Scholar
  15. 15.
    Warnock GL, Kneteman NM, Ryan E, et al.: Normoglycemia after transplantation of freshly isolated and cryopreserved pancreatic islets in type 1 (insulin-dependent) diabetes mellitus. Diabetologia 1991, 34:55–58.CrossRefPubMedGoogle Scholar
  16. 16.
    Ar’Rajab A, Ahrén B, Bengmark S: Insulin and glucagon secretion in streptozotocin diabetic rats: influences of islet transplanted to the renal subcapsular space. Diabetes Res 1989, 12:37–41.PubMedGoogle Scholar
  17. 17.
    Ar’Rajab A, Ahrén B, Alumets J, Bengmark S: Islet transplantation to the renal subcapsular space in streptozotocin diabetic rats: long-term effects on insulin and glucagon secretion. Acta Chir Scand 1989, 155:503–508.PubMedGoogle Scholar
  18. 18.
    Ar’Rajab A, Ahrèn B: Effects of yohimbine and nicotinic acid on glucose stimulated insulin secretion after islet transplantation in streptozotocin diabetic rats. Diabetes Res Clin Pract 1990, 11:81–87.CrossRefGoogle Scholar
  19. 19.
    Ar’Rajab A, Ahrén B, Alumets J, et al.: Islet transplantation to the renal subcapsular space improves late complications in streptozotocin diabetic rats. Eur Surg Res 1990, 22:270–278.CrossRefPubMedGoogle Scholar
  20. 20.
    Carlsson PO, Palm F, Andersson A, Liss P: Chronically decreased oxygen tension in rat pancreatic islets transplanted under the kidney capsule. Transplantation 2000, 69:761–766.CrossRefPubMedGoogle Scholar
  21. 21.
    Carlsson PO, Palm F, Andersson A, Liss P: Markedly decreased oxygen tension in transplanted rat pancreatic islets irrespective of the implantation site. Diabetes 2001, 50:489–495.CrossRefPubMedGoogle Scholar
  22. 22.
    Kaufman DB, Morel P, Field MJ, et al.: Purified canine islet autografts. Functional outcome as influenced by islet number and implantation site. Transplantation 1990, 50:385–391.CrossRefPubMedGoogle Scholar
  23. 23.
    • Rajab A, Buss J, Diakoff E, et al.: Comparison of the portal vein and kidney subcapsule as sites for primate islet auto-transplantation. Cell Transplant 2008, 17:1015–1023. This article compared the portal vein to the kidney subcapsule in a primate model.CrossRefPubMedGoogle Scholar
  24. 24.
    Jindal RM, Sidner RA, McDaniel HB, et al.: Intraportal vs kidney subcapsular site for human pancreatic islet transplantation. Transplant Proc 1998, 30:398–399.CrossRefPubMedGoogle Scholar
  25. 25.
    Gray DW: Islet isolation and transplantation techniques in the primate. Surg Gynecol Obstet 1990, 170:225–232.PubMedGoogle Scholar
  26. 26.
    Alderson D, Walsh TN, Farndon JR: Islet cell transplantation in diabetic dogs: studies of graft function and storage. Br J Surg 1984, 71:756–760.CrossRefPubMedGoogle Scholar
  27. 27.
    Largiader F, Kolb E, Binswanger U, Illig R: [Successful allotransplantation of an island of Langerhans] [in German]. Schweiz Med Wochenschr 1979, 109:1733–1736.PubMedGoogle Scholar
  28. 28.
    Stagner J, Ahren B, Sundler F, White K: Reconstructing the pancreas: restoration of normoglycemia, exocrine function, and islet innervation by islet transplantation to the pancreas. Transplant Proc 2008, 40:452–454.CrossRefPubMedGoogle Scholar
  29. 29.
    Liebermann-Meffert D, White H, Vaubel E, eds: The Greater Omentum: Anatomy, Physiology, Pathology, Surgery, with an Historical Survey. Berlin: Springer-Verlag; 1983.Google Scholar
  30. 30.
    Kin T, Korbutt GS, Rajotte RV: Survival and metabolic function of syngeneic rat islet grafts transplanted in the omental pouch. Am J Transplant 2003, 3:281–285.CrossRefPubMedGoogle Scholar
  31. 31.
    al-Abdullah IH, Anil Kumar MS, Kelly-Sullivan D, Abouna GM: Site for unpurified islet transplantation is an important parameter for determination of the outcome of graft survival and function. Cell Transplant 1995, 4:297–305.Google Scholar
  32. 32.
    Ao Z, Matayoshi K, Lakey JR, et al.: Survival and function of purified islets in the omental pouch site of outbred dogs. Transplantation 1993, 56:524–529.CrossRefPubMedGoogle Scholar
  33. 33.
    Gustavson SM, Rajotte RV, Hunkeler D, et al.: Islet auto-transplantation into an omental or splenic site results in a normal beta cell but abnormal alpha cell response to mild non-insulin-induced hypoglycemia. Am J Transplant 2005, 5:2368–2377.CrossRefPubMedGoogle Scholar
  34. 34.
    •• Berman DM, O’Neil JJ, Coffey LC, et al.: Long-term survival of nonhuman primate islets implanted in an omental pouch on a biodegradable scaffold. Am J Transplant 2009, 9:91–104. This article described the outcome of islets transplanted into the omental pouch of primates.CrossRefPubMedGoogle Scholar
  35. 35.
    Ferguson J, Scothorne RJ: Further studies on the transplantation of isolated pancreatic islets. J Anat 1977, 124(Pt 1):9–20.PubMedGoogle Scholar
  36. 36.
    Ao Z, Matayoshi K, Yakimets WJ, Katyal D, et al.: Development of an omental pouch site for islet transplantation. Transplant Proc 1992, 24:2789.PubMedGoogle Scholar
  37. 37.
    Sageshima J, Kirchhof N, Shibata S, et al.: Small bowel subserosal space as a site for islet transplantation and local drug delivery. Transplant Proc 2001, 33(1–2):1710.CrossRefPubMedGoogle Scholar
  38. 38.
    Xiaohui T, Wujun X, Xiaoming D, et al.: Small intestinal submucosa improves islet survival and function in vitro culture. Transplant Proc 2006, 38:1552–1558.CrossRefPubMedGoogle Scholar
  39. 39.
    Caiazzo R, Gmyr V, Hubert T, et al.: Evaluation of alternative sites for islet transplantation in the minipig: interest and limits of the gastric submucosa. Transplant Proc 2007, 39:2620–2623.CrossRefPubMedGoogle Scholar
  40. 40.
    Tchervenivanov N, Yuan S, Lipsett M, et al.: Morphological and functional studies on submucosal islet transplants in normal and diabetic hamsters. Cell Transplant 2002, 11:529–537.PubMedGoogle Scholar
  41. 41.
    • Wszola M, Berman A, Fabisiak M, et al.: TransEndoscopic Gastric SubMucosa Islet Transplantation (eGSM-ITx) in pigs with streptozotocine induced diabetes - technical aspects of the procedure - preliminary report. Ann Transplant 2009, 14:45–50. This article describes the techniques of endoscopic islet transplantation into the gastric submucosa in pigs.PubMedGoogle Scholar
  42. 42.
    Juang JH, Hsu BR, Kuo CH: Islet transplantation at subcutaneous and intramuscular sites. Transplant Proc 2005, 37:3479–3481.CrossRefPubMedGoogle Scholar
  43. 43.
    Balamurugan AN, Gu Y, Tabata Y, et al.: Bioartificial pancreas transplantation at prevascularized intermuscular space: effect of angiogenesis induction on islet survival. Pancreas 2003, 26:279–285.CrossRefPubMedGoogle Scholar
  44. 44.
    • Witkowski P, Sondermeijer H, Hardy MA, et al.: Islet grafting and imaging in a bioengineered intramuscular space. Transplantation 2009, 88:1065–1074. This article describes a bioengineered intramuscular site for islet transplantation.CrossRefPubMedGoogle Scholar
  45. 45.
    Pileggi A, Molano RD, Ricordi C, et al.: Reversal of diabetes by pancreatic islet transplantation into a subcutaneous, neovascularized device. Transplantation 2006, 81:1318–1324.CrossRefPubMedGoogle Scholar
  46. 46.
    Stegall MD: Monitoring human islet allografts using a forearm biopsy site. Ann Transplant 1997, 2:8–11.PubMedGoogle Scholar
  47. 47.
    Salazar-Bañuelos A, Wright J, Sigalet D, Benítez-Bribiesca L: The bone marrow as a potential receptor site for pancreatic islet grafts. Arch Med Res 2008, 39:139–141.CrossRefPubMedGoogle Scholar
  48. 48.
    • Cantarelli E, Melzi R, Mercalli A, et al.: Bone marrow as an alternative site for islet transplantation. Blood 2009, 114:4566–4574. This article describes the use of bone marrow as a site for islet transplantation.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.The Comprehensive Transplant CenterThe Ohio State UniversityColumbusUSA

Personalised recommendations