DCD for Islet Transplantation

  • Takashi Kenmochi
  • Takehide Asano
  • Naotake Akutsu
  • Taihei Ito


Pancreatic islet transplantation has the potential to become the most physiologically advantageous and minimally invasive procedure for the treatment of type 1 diabetes mellitus. Since the first clinical islet transplantation was performed at the University of Minnesota in 1974 [1], the results have been far from ideal for more than two decades in spite of an improvement of islet isolation technique by Ricordi et al. [2–4]. The introduction of the Edmonton protocol, with a highly improved rate of insulin independency, encouraged us to promote clinical islet transplantation [5, 6]. In Japan, we organized the Working Group (The Japanese Islet Transplant Registry) in 1997 under the Japanese Society for Pancreas and Islet Transplantation for the purpose of starting clinical islet transplantation. The first issue of the Working Group was to construct a system of clinical islet transplantation in Japan including the registration of the recipients, procurement of the pancreas for islet isolation and transplantation of the isolated islets. In Japan, afterwards, various problems facing to a start of clinical islet transplantation have been discussed and we completed the guideline for clinical islet transplantation in Japan. The Japanese Organ Transplant Law was enforced in 1997 and organ transplantations using brain dead (DBD) donors were finally started. Since the islet transplantation was not included in the Japanese Organ Transplant Law because it was categorized as tissue transplantation, we were able to use the pancreas only from DCD donors for islet transplantation. The first islet isolation from the human pancreas was performed in 2003.9 and the first islet transplantation was performed in 2004.4 [7–9]. Sixty-five islet isolations and 34 islet transplantations were performed in our country from 2003.9.12 to 2007.3.11 [10].

In this chapter, we describe the current status of clinical islet transplantation using DCD donors in Japan.


Islet Transplantation Warm Ischemic Time Islet Isolation Insulin Independency Hypoglycemic Unawareness 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Najarian JS, Sutherland DE, Matas AJ, Steffes MW, Simmons RL, Goetz FC. Human islet transplantation: a preliminary report. Transplant Proc. 1977;9:233–6.PubMedGoogle Scholar
  2. 2.
    International Islet Transplant Registry. Newsletter No. 8. 1999.Google Scholar
  3. 3.
    Ricordi C, Finke EH, Lacy PE. A method for the mass isolation of islets from the adult pig pancreas. Diabetes. 1986;35:649–53.PubMedCrossRefGoogle Scholar
  4. 4.
    Ricordi C, Lacy PE, Finke EH, Olack BJ, Scharp DW. Automated method for isolation of human pancreatic islets. Diabetes. 1988;37:413–20.PubMedCrossRefGoogle Scholar
  5. 5.
    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. N Engl J Med. 2000;343:230–8.PubMedCrossRefGoogle Scholar
  6. 6.
    Ryan EA, Lakey JR, Rajotte RV, Korbutt GS, Kin T, Imes S, et al. Clinical outcomes and insulin secretion after islet transplantation with the Edmonton protocol. Diabetes. 2001;50:710–9.PubMedCrossRefGoogle Scholar
  7. 7.
    Matsumoto S, Okitsu T, Iwanaga Y, Noguchi H, Nagata H, Yonekawa Y, et al. Successful islet transplantation from nonheartbeating donor pancreata using modified Ricordi islet isolation method. Transplantation. 2006;82:460–5.PubMedCrossRefGoogle Scholar
  8. 8.
    Matsumoto S, Tanaka K. Pancreatic islet cell transplantation. J Hepatobiliary Pancreat Surg. 2005;12:227–30.PubMedCrossRefGoogle Scholar
  9. 9.
    Saito T, Ise K, Sato Y, Gotoh M, Matsumoto S, Kenmochi T, et al. The start of an islet transplantation program in Japan. Transplant Proc. 2005;37:3424–6.PubMedCrossRefGoogle Scholar
  10. 10.
    Kenmochi T, Asano T, Maruyama M, Saigo K, Akutsu N, Iwashita C, Ohtsuki K, Ito T. Clinical islet transplantation in Japan. J Hepatobiliary Pancreat Surg. 2009;16(2):124–30.PubMedCrossRefGoogle Scholar
  11. 11.
    Japanese Society of Tissue Transplantation (JSTT) ed. Guideline on the safety, storage, and application of human tissue in medical practice. IV. Criteria for donor screening.
  12. 12.
    Kootstra G, Daemen J, Oomen A. Categories of non-heart-beating donors. Transplant Proc. 1995;27:2893–4.PubMedGoogle Scholar
  13. 13.
    Sanchez-Fructuoso A, et al. Renal transplantation from non-heart-beating donors: a promising alternative to enlarge the donor pool. J Am Soc Nephrol. 2000;11:350–8.PubMedGoogle Scholar
  14. 14.
    Arita S, Asano T, Kenmochi T, Enomoto K, Isono K. An initial wash-out solution for “in situ machine wash-out”. Transplant Proc. 1991;23:2589.PubMedGoogle Scholar
  15. 15.
    Asano T, Enomoto K, Ohtsuka M, Goto T, Nakagohri T, Kenmochi T, Ochiai T, Isono K. Usefulness of rapid machine cooling in the procurement of livers. Transplant Proc. 1989;21(1 Pt 2):1307–8.PubMedGoogle Scholar
  16. 16.
    Goto T, Tanioka Y, Sakai T, Terai S, Kamoda Y, Li S, et al. Application of the two-layer method on pancreas digestion results in improved islet yield and maintained viability of isolated islets. Transplantation. 2007;27:754–8.CrossRefGoogle Scholar
  17. 17.
    Kin T, Mirbolooki M, Salehi P, Tsukada M, O'Gorman D, Imes S, et al. Islet isolation and transplantation outcomes of pancreas preserved with University of Wisconsin solution versus two-layer method using preoxygenated perfluorocarbon. Transplantation. 2006;82:1286–90.PubMedCrossRefGoogle Scholar
  18. 18.
    Takahashi T, Tanioka Y, Matsuda T, Toyama H, Kakinoki K, Li S, et al. Impact of the two-layer method on the quality of isolated pancreatic islets. Hepatogastroenterology. 2006;53:179–82.PubMedGoogle Scholar
  19. 19.
    Tanaka T, Suzuki Y, Tanioka Y, Sakai T, Kakinoki K, Goto T, et al. Possibility of islet transplantation from a nonheartbeating donor pancreas resuscitated by the two-layer method. Transplantation. 2005;80:738–42.PubMedCrossRefGoogle Scholar
  20. 20.
    Tsujimura T, Kuroda Y, Churchill TA, Avila JG, Kin T, Shapiro AM, et al. Short-term storage of the ischemically damaged human pancreas by the two-layer method prior to islet isolation. Cell Transplant. 2004;13:67–73.PubMedGoogle Scholar
  21. 21.
    Tsujimura T, Kuroda Y, Kin T, Avila JG, Rajotte RV, Korbutt GS, et al. Human islet transplantation from pancreases with prolonged cold ischemia using additional preservation by the two-layer (UW solution/perfluorochemical) cold-storage method. Transplantation. 2002;74:1687–91.PubMedCrossRefGoogle Scholar
  22. 22.
    Tanioka Y, Sutherland DE, Kuroda Y, Gilmore TR, Asaheim TC, Kronson JW, et al. Excellence of the two-layer method (University of Wisconsin solution/perfluorochemical) in pancreas preservation before islet isolation. Surgery. 1997;122:435–42.PubMedCrossRefGoogle Scholar
  23. 23.
    Caballero-Corbalán J, Eich T, Lundgren T, Foss A, Felldin M, Källen R, et al. No beneficial effect of two-layer storage compared with UW-storage on human islet isolation and transplantation. Transplantation. 2007;84:864–9.PubMedCrossRefGoogle Scholar
  24. 24.
    Sawada T, Matsumoto I, Nakano M, Kirchhof N, Sutherland DE, Hering BJ. Improved islet yield and function with ductal injection of University of Wisconsin solution before pancreas preservation. Transplantation. 2003;75(12):1965–9.PubMedCrossRefGoogle Scholar
  25. 25.
    Matsumoto S, Noguichi H, Shimoda M, Ikemoto T, Naziruddin B, Jackson A, Tamura Y, Olson G, Fujita Y, Chujo D, Takita M, Kobayashi N, Onaca N, Levy M. Seven consecutive successful clinical islet isolations with pancreatic ductal injection. Cell Transplant. 2010;19(3):291–7.PubMedCrossRefGoogle Scholar
  26. 26.
    Anazawa T, Balamurugan AN, Papas KK, Avgoustiniatos ES, Ferrer J, Matsumoto S, Sutherland DE, Hering BJ. Improved method of porcine pancreas procurement with arterial flush and ductal injection enhances islet isolation outcome. Transplant Proc. 2010;42(6):2032–5.PubMedCentralPubMedCrossRefGoogle Scholar
  27. 27.
    Shimoda M, Itoh T, Sugimoto K, Iwahashi S, Takita M, Chujo D, Sorelle JA, Naziruddin B, Levy MF, Grayburn PA, Matsumoto S. Improvement of collagenase distribution with the ductal preservation for human islet isolation. Islets. 2012;4(2):130–7.PubMedCentralPubMedCrossRefGoogle Scholar
  28. 28.
    Kenmochi T, Matsumoto S, Tanioka Y, Saito T, Ono J, Okamoto M, et al. Manual for clinical islet transplantation in Japan, 3rd ed. In: Fukushima H, editor. The Japanese Society for Pancreas and Islet Transplantation. Fukushima, Japan; 2006. p. 1–55.Google Scholar
  29. 29.
    Ricordi C, Gray DWR, Hering BJ, et al. Islet isolation assessment in man and large animals. Acta Diabetol Lat. 1990;27:185–95.PubMedCrossRefGoogle Scholar
  30. 30.
    Gray DWR, McShane P, Grant A, Morris PJ. A method for isolation of islets of Langerhans from the human pancreas. Diabetes. 1984;33:1055–61.PubMedCrossRefGoogle Scholar
  31. 31.
    Andersson A, Borg H, Groth CG, et al. Survival of isolated human islets of Langerhans maintained in tissue culture. J Clin Invest. 1976;57:1295–301.PubMedCentralPubMedCrossRefGoogle Scholar
  32. 32.
    Ashcroft SJH, Bassett JM, Rndle PJ. Isolation of human pancreatic islets capable of releasing insulin and metabolizing glucose in vitro. Lancet. 1971;1:888–9.PubMedCrossRefGoogle Scholar
  33. 33.
    Ballinger WF, Lacy PE. Transplantation of intact pancreatic islets in rats. Surgery. 1972;72:175–86.PubMedGoogle Scholar
  34. 34.
    Sutherland DE, Matas AJ, Steffes MW, Najarian JS. Infant human pancreas. A potential source of islet tissue for transplantation. Diabetes. 1976;25(12):1123–8.PubMedCrossRefGoogle Scholar
  35. 35.
    Davalli AM, Ricordi C, Socci C, Braghi S, Bertuzzi F, Fattor B, Di Carlo V, Pontiroli AE, Pozza G. Abnormal sensitivity to glucose of human islets cultured in a high glucose medium: partial reversibility after an additional culture in a normal glucose medium. J Clin Endocrinol Metab. 1991;72(1):202–8.PubMedCrossRefGoogle Scholar
  36. 36.
    Kneteman NM, Rajotte RV. Isolation and cryopreservation of human pancreatic islets. Life Support Syst. 1985;3 Suppl 1:712–8.PubMedGoogle Scholar
  37. 37.
    Scharp DW, Lacy PE, Finke E, Olack B. Low-temperature culture of human islets isolated by the distention method and purified with Ficoll or Percoll gradients. Surgery. 1987;102(5):869–79.PubMedGoogle Scholar
  38. 38.
    Povlsen CO, Skakkebaek NE, Rygaard J, Jensen G. Heterotransplantation of human foetal organs to the mouse mutant nude. Nature. 1974;248(445):247–9.PubMedCrossRefGoogle Scholar
  39. 39.
    Usadel KH, Schwedes U, Bastert G, Steinau U, Klempa I, Fassbinder W, Schöffling K. Transplantation of human fetal pancreas: experience in thymusaplastic mice and rats and in a diabetic patient. Diabetes. 1980;29 Suppl 1:74–9.PubMedCrossRefGoogle Scholar
  40. 40.
    Saito T, Gotoh M, Satomi S, Uemoto S, Kenmochi T, Itoh T, Kuroda Y, Yasunami Y, Matsumoto S, Teraoka S, Working Members of the Japanese Pancreas and Islet Transplantation Association. Islet transplantation using donors after cardiac death: report of the Japan islet transplantation registry. Transplantation. 2010;90(7):740–7.PubMedCrossRefGoogle Scholar
  41. 41.
    Kenmochi T, Asano T, Jingu K, Matsui Y, Maruyama M, Akutsu N, et al. Effectiveness of hydroxyethyl starch (HES) on purification of pancreatic islets. J Surg Res. 2003;111:16–22.PubMedCrossRefGoogle Scholar
  42. 42.
    Kenmochi T, Asano T, Jingu K, Matsui Y, Maruyama M, Miyauchi H, et al. Purification of pancreatic islets using hydroxyethyl starch-Collins solution. Transplant Proc. 2001;33:670–1.PubMedCrossRefGoogle Scholar
  43. 43.
    Kenmochi T, Miyamoto M, Une S, Nakagawa Y, Moldovan S, Navarro RA, et al. Improved quality and yield of islets isolated from human pancreata using a two-step digestion method. Pancreas. 2000;20:184–90.PubMedCrossRefGoogle Scholar
  44. 44.
    Kenmochi T, Asano T, Jingu K, Iwashita C, Miyauchi H, Takahashi S, et al. Development of a fully automated islet digestion system. Transplant Proc. 2000;32:341–3.PubMedCrossRefGoogle Scholar
  45. 45.
    Mullen Y, Arita S, Kenmochi T, Une S, Smith CV. A two-step digestion process and lap-1 cold preservation solution for human islet isolation. Ann Transplant. 1998;2:40–5.Google Scholar
  46. 46.
    Kenmochi T, Miyamoto M, Sasaki H, Une S, Nakagawa Y, Moldovan S, et al. Lap-1 cold preservation solution for isolation of high-quality human pancreatic islets. Pancreas. 1998;17:367–77.PubMedCrossRefGoogle Scholar
  47. 47.
    Iwashita C, Asano T, Kenmochi T, Jingu K, Uematsu T, Nakagohri T, et al. Combined method of mechanical chopper and automated two-step digestion technique for islet isolation from canine pancreas. Transplant Proc. 1996;28:337–8.PubMedGoogle Scholar
  48. 48.
    Jingu K, Asano T, Kenmochi T, Enomoto K, Uematsu T, Nakagohri T, et al. Combined method of mechanical chopper and automated digestion system for islet isolation. Transplant Proc. 1996;26:634–6.Google Scholar

Copyright information

© Springer Japan 2014

Authors and Affiliations

  • Takashi Kenmochi
    • 1
  • Takehide Asano
    • 2
  • Naotake Akutsu
    • 2
  • Taihei Ito
    • 1
  1. 1.Department of Organ Transplant SurgeryFujita Health UniversityToyoake CityJapan
  2. 2.Department of Surgery and Clinical Research CenterChiba-East National HospitalChiba CityJapan

Personalised recommendations