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Pancreatic islet cell transplantation using non-heart-beating donors (NHBDs)

  • Published:
Journal of Hepato-Biliary-Pancreatic Surgery

Abstract

Recent dramatic improvements in clinical islet cell transplantation demonstrated by the Edmonton group have increased the demand for this treatment, and donor shortage could become a major problem. Utilization of marginal donors could alleviate the donor shortage, and non-heart-beating donors (NHBDs) might be good resources. The University of Pennsylvania group demonstrated that it was possible to isolate islets from NHBDs, and the group actually transplanted islets from NHBDs, for the first time. The patient became insulin-independent; however, there had been no more cases using NHBDs until our group initiated islet transplantations from NHBDs in Japan. In order to utilize NHBDs effectively, we modified the standard islet isolation method. These modifications included minimizing the warm ischemic time, the use of trypsin inhibition during isolation, carrying out density measurement before purification and the use of a less toxic islet purification solution. With these modifications we were able to transplant nine of ten islet preparations from ten NHBDs (90%), into five type-1 diabetic patients. The first transplantation was performed on April 7, 2004 (the first time in Japan), and this patient became insulin-independent after the second islet transplantation (first time in Japan). All patients showed improved glycemic control and reduced insulin requirements, without hypoglycemic events. We also performed living-donor islet transplantation, with our modified islet isolation protocol, on January 19, 2005. The improved islet isolation protocol enabled us to perform effective islet transplantations from NHBDs, and it also enabled us to perform the living-donor islet transplantation.

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References

  1. JP Boyle AA Honeycutt KM Narayan TJ Hoerger LS Geiss H Chen TJ Thompson (2001) ArticleTitleProjection of diabetes burden through 2050: impact of changing demography and disease prevalence in the US Diabetes Care 24 1936–1940 Occurrence Handle1:STN:280:DC%2BD3MrntF2jsA%3D%3D Occurrence Handle11679460

    CAS  PubMed  Google Scholar 

  2. InstitutionalAuthorNameDCCT Res Group (1990) ArticleTitleDiabetes Control and Complications Trial (DCCT) Update: Diabetes Care 13 427–433

    Google Scholar 

  3. InstitutionalAuthorNameDCCT Res Group (1995) ArticleTitleAdverse events and their association with treatment regimens in the Diabetes Control and Complications Trial Diabetes Care 18 1415–1427

    Google Scholar 

  4. JM Venstrom MA McBride KI Rother B Hirshberg TJ Orchard DM Harlan (2003) ArticleTitleSurvival after pancreas transplantation in patients with diabetes and preserved kidney function JAMA 290 2817–2823 Occurrence Handle1:CAS:528:DC%2BD3sXps1Cru7w%3D Occurrence Handle14657065

    CAS  PubMed  Google Scholar 

  5. B Hering C Ricordi (1999) ArticleTitleIslet transplantation for patients with type 1 diabetes: results, research priorities, and reasons for optimism Graft 2 12–27

    Google Scholar 

  6. AM Shapiro JR Lakey EA Ryan GS Korbutt E Toth GL Warnock NM Kneteman RV Rajotte (2000) ArticleTitleIslet transplantation in seven patients with type 1 diabetes mellitus using a glucocorticoid-free immunosuppressive regimen N Engl J Med 343 230–238 Occurrence Handle1:CAS:528:DC%2BD3cXlvVSmt7k%3D Occurrence Handle10911004

    CAS  PubMed  Google Scholar 

  7. KI Rother DM Harlan (2004) ArticleTitleChallenges facing islet transplantation for the treatment of type 1 diabetes mellitus J Clin Invest 114 877–883 Occurrence Handle1:CAS:528:DC%2BD2cXot12gsb4%3D Occurrence Handle15467822

    CAS  PubMed  Google Scholar 

  8. DA Baidal T Froud JV Ferreira A Khan R Alejandro C Ricordi (2003) ArticleTitleThe bag method for islet cell infusion Cell Transplant 12 809–813 Occurrence Handle14653627

    PubMed  Google Scholar 

  9. S Matsumoto S Qualley S Goel D Hagman I Sweet V Poitout DM Strong RP Robertson JA Reems (2002) ArticleTitleEffect of the two-layer (University of Wisconsin solution — perfluorochemical plus O2) method of pancreas preservation on human islet isolation, as assessed by the Edmonton Isolation Protocol Transplantation 74 1414–1419 Occurrence Handle1:CAS:528:DC%2BD38XptVSiurg%3D Occurrence Handle12451242

    CAS  PubMed  Google Scholar 

  10. S Matsumoto T Rigley S Qualley Y Kuroda J Reems R Stevens (2002) ArticleTitleEfficacy of the oxygen-charged static two-layer method for short-term pancreas preservation and islet isolation from nonhuman primate and human pancreata Cell Transplant 11 769–777 Occurrence Handle12588109

    PubMed  Google Scholar 

  11. T Sawada I Matsumoto M Nakano N Kirchhof DE Sutherland BJ Hering (2003) ArticleTitleImproved islet yield and function with ductal injection of University of Wisconsin solution before pancreas preservation Transplantation 75 1965–1969 Occurrence Handle12829895

    PubMed  Google Scholar 

  12. JR Lakey LM Helms T Kin GS Korbutt RV Rajotte AM Shapiro GL Warnock (2001) ArticleTitleSerine-protease inhibition during islet isolation increases islet yield from human pancreases with prolonged ischemia Transplantation 72 565–570 Occurrence Handle1:CAS:528:DC%2BD3MXntFKhsr0%3D Occurrence Handle11544413

    CAS  PubMed  Google Scholar 

  13. S Matsumoto T Rigley J Reems Y Kuroda R Stevens (2003) ArticleTitleImproved islet yields from Macaca nemestrina and marginal human pancreata after two-layer method preservation and endogenous trypsin inhibition Am J Transplant 3 53–63 Occurrence Handle1:CAS:528:DC%2BD3sXotFCisw%3D%3D

    CAS  Google Scholar 

  14. S Matsumoto HJ Zhang T Gilmore MP van der Burg DER Sutherland BJ Hering (1998) ArticleTitleLarge-scale isopycnic islet purification utilizing non-toxic, endotoxin-free media facilitates immediate single-donor pig islet allograft function Transplantation 66 S30

    Google Scholar 

  15. MP der Burg I Basir E Bouwman (1998) ArticleTitleNo porcine islet loss during density gradient purification in a novel iodixanol in University of Wisconsin solution Transplant Proc 30 362–363 Occurrence Handle9532080

    PubMed  Google Scholar 

  16. MP Corlett DW Scharp (1988) ArticleTitleThe effect of pancreatic warm ischemia on islet isolation in rats and dogs J Surg Res 45 531–536 Occurrence Handle1:STN:280:BiaD3sflt1Y%3D Occurrence Handle3054326

    CAS  PubMed  Google Scholar 

  17. Y Tanioka BJ Hering DE Sutherland JW Kronson Y Kuroda TR Gilmore TC Aasheim MC Rusten JP Leone (1997) ArticleTitleEffect of pancreatic warm ischemia on islet yield and viability in dogs Transplantation 64 1637–1641 Occurrence Handle1:STN:280:DyaK1c%2Fot1ymtQ%3D%3D Occurrence Handle9422394

    CAS  PubMed  Google Scholar 

  18. R Stevens S Matsumoto O Lawrence TH Rigley CL Marh (2001) ArticleTitleIschemically damaged primate pancreases (Px) can be resuscitated by the two-layer method before islet isolation: implications for clinical islet transplantation Am J Transplant 1 S321

    Google Scholar 

  19. T Deai Y Tanioka Y Suzuki Y Kuroda (1999) ArticleTitleThe effect of the two-layer cold storage method on islet isolation from ischemically damaged pancreas Kobe J Med Sci 45 191–199 Occurrence Handle1:STN:280:DC%2BD3c3hsFOksA%3D%3D Occurrence Handle10752312

    CAS  PubMed  Google Scholar 

  20. HL Rilo PB Carroll M Trucco J Phipps G Trucco D Finegold C Ricordi (1994) ArticleTitleHuman pancreatic islet isolation from a diabetic non-heart-beating donor Transplant Proc 26 598 Occurrence Handle1:STN:280:ByuB38rkvVA%3D Occurrence Handle8171575

    CAS  PubMed  Google Scholar 

  21. HA Clayton SM Swift JM Turner RF James PR Bell (2000) ArticleTitleNon-heart-beating organ donors: a potential source of islets for transplantation? Transplantation 69 2094–2098 Occurrence Handle1:STN:280:DC%2BD3czgvFCnsQ%3D%3D Occurrence Handle10852603

    CAS  PubMed  Google Scholar 

  22. JF Markmann S Deng NM Desai X Huang E Velidedeoglu A Frank C Liu KL Brayman MM Lian B Wolf E Bell M Vitamaniuk N Doliba F Matschinsky E Markmann CF Barker A Naji (2003) ArticleTitleThe use of non-heart-beating donors for isolated pancreatic islet transplantation Transplantation 75 1423–1429 Occurrence Handle12792491

    PubMed  Google Scholar 

  23. S Matsumoto K Tanaka DM Strong JA Reems (2004) ArticleTitleEfficacy of human islet isolation from the tail section of the pancreas for the possibility of living donor islet transplantation Transplantation 78 839–843 Occurrence Handle15385802

    PubMed  Google Scholar 

  24. M Miyamoto Y Morimoto AN Balamurugan Y Kawakami Y Gu A Satake Y Suzuki Y Tanioka Y Kuroda N Shimizu T Tohyama Y Nozawa M Nozawa K Inoue (2000) ArticleTitleImprovement of modified two-layer preservation method (PFC/Kyoto solution) in islet isolation from breeder pigs Transplant Proc 32 1660–1661 Occurrence Handle1:CAS:528:DC%2BD3cXovFKis7w%3D Occurrence Handle11119879

    CAS  PubMed  Google Scholar 

  25. CJ Liu T Bando T Hirai T Hirata K Yagi H Yokomise K Inui S Hitomi H Wada (1995) ArticleTitleImproved 20-hour canine lung preservation with a new solution — ET-Kyoto solution Eur J Cardiothorac Surg 9 548–552 Occurrence Handle1:STN:280:BymC38fjsV0%3D Occurrence Handle8562098

    CAS  PubMed  Google Scholar 

  26. H Yoshida H Okuno T Kamoto T Habuchi Y Toda S Hasegawa T Nakamura H Wada O Ogawa S Yamamoto (2002) ArticleTitleComparison of the effectiveness of ET-Kyoto with Euro-Collins and University of Wisconsin solutions in cold renal storage Transplantation 74 1231–1236 Occurrence Handle1:CAS:528:DC%2BD38XptVSiu7Y%3D Occurrence Handle12451258

    CAS  PubMed  Google Scholar 

  27. A Heiser K Ulrichs W Muller-Ruchholtz (1994) ArticleTitleIsolation of porcine pancreatic islets: low trypsin activity during the isolation procedure guarantees reproducible high islet yields J Clin Lab Anal 8 407–411 Occurrence Handle1:CAS:528:DyaK2MXivFSmtb0%3D Occurrence Handle7869180

    CAS  PubMed  Google Scholar 

  28. NL Rose MM Palcic LM Helms JR Lakey (2003) ArticleTitleEvaluation of Pefabloc as a serine protease inhibitor during human-islet isolation Transplantation 75 462–466 Occurrence Handle1:CAS:528:DC%2BD3sXhsVykurg%3D Occurrence Handle12605110

    CAS  PubMed  Google Scholar 

  29. NL Rose MM Palcic AM Shapiro JR Lakey (2004) ArticleTitleEndogenous pancreatic enzyme activity levels show no significant effect on human islet isolation yield Cell Transplant 13 153–160 Occurrence Handle15129761

    PubMed  Google Scholar 

  30. GS Robertson DR Chadwick J Davies S Rose H Contractor RF James PR Bell NJ London (1994) ArticleTitleThe effectiveness of components of University of Wisconsin solution in improving human pancreatic islet purification Transplantation 57 346–354 Occurrence Handle1:CAS:528:DyaK2cXltVentbg%3D Occurrence Handle8108869

    CAS  PubMed  Google Scholar 

  31. S Matsumoto (2004) ArticleTitleIslet transplantation for severe diabetes mellitus (in Japanese) Shinro to Shinyaku (Medical Consultation and New Remedies) 41 891

    Google Scholar 

  32. Matsumoto S, Okitsu T, Iwanaga Y, Noguchi H, Yonekawa Y, Nagata H, Yamada Y, Shibata T, Kasai Y, Maekawa T, Tanaka K (2004) Successful islet transplantation from non-heart beating donor pancreata in Japan. In: The 15th international symposium on molecular biology and hematopoiesis (abstract) Symposium-3. 2004 Aug 6–7; Tokyo, Japan

  33. S Matsumoto T Okitsu Y Iwanaga H Noguchi H Nagata Y Yonekawa Y Yamada K Fukuda K Tsukiyama H Suzuki Y Kawasaki M Shimodaira K Matsuoka T Shibata Y Kasai T Maekawa J Shapiro K Tanaka (2005) ArticleTitleInsulin independence after living-donor distal pancreatectomy and islet allotrans-plantation Lancet 365 1642–1644 Occurrence Handle1:CAS:528:DC%2BD2MXktVGku70%3D Occurrence Handle15889479

    CAS  PubMed  Google Scholar 

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Matsumoto, S., Tanaka, K. Pancreatic islet cell transplantation using non-heart-beating donors (NHBDs). J Hepatobiliary Pancreat Surg 12, 227–230 (2005). https://doi.org/10.1007/s00534-005-0978-z

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  • DOI: https://doi.org/10.1007/s00534-005-0978-z

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