Skip to main content
SpringerLink
Log in
Book cover

Contemporary Pancreas Transplantation pp 1–25Cite as

Islet Cell Transplant

  • Living reference work entry
  • Latest version View entry history
  • First Online:

Part of the book series: Organ and Tissue Transplantation ((OTT))

Abstract

Exogenous insulin administration is currently the only treatment available for patients with type 1 diabetes, but it is not a cure. Long-term complications associated with the disease may be preventable with a treatment strategy that can provide better blood glucose control. The transplantation of isolated islets provides the potential to restore endogenous insulin production and reestablish normoglycemia. Significant progress has been made in the outcomes of clinical islet transplantation, reflecting improvements in nondiabetogenic immunosuppression and preparation of sufficient quantities of highly viable islets for transplantation. Islet transplantation represents a potential cure for patients with type 1 diabetes.

This is a preview of subscription content, log in via an institution.

References

  • Agarwal A, Brayman KL (2012) Update on islet cell transplantation for type 1 diabetes. Semin Interv Radiol 29(2):90–98

    Article  Google Scholar 

  • Alipio Z, Liao W, Roemer EJ, Waner M, Fink LM, Ward DC, Ma Y (2010) Reversal of hyperglycemia in diabetic mouse models using induced-pluripotent stem (iPS)-derived pancreatic beta-like cells. Proc Natl Acad Sci U S A 107(30):13426–13431

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Anazawa T, Balamurugan AN, Bellin M, Zhang HJ, Matsumoto S, Yonekawa Y, Tanaka T, Loganathan G, Papas KK, Beilman GJ, Hering BJ, Sutherland DE (2009) Human islet isolation for autologous transplantation: comparison of yield and function using SERVA/Nordmark versus Roche enzymes. Am J Transplant 9(10):2383–2391

    Article  CAS  PubMed  Google Scholar 

  • Anazawa T, Matsumoto S, Yonekawa Y, Loganathan G, Wilhelm JJ, Soltani SM, Papas KK, Sutherland DE, Hering BJ, Balamurugan AN (2011) Prediction of pancreatic tissue densities by an analytical test gradient system before purification maximizes human islet recovery for islet autotransplantation/allotransplantation. Transplantation 91(5):508–514

    Article  PubMed  Google Scholar 

  • Andersson A, Borg H, Hallberg A, Hellerstrom C, Sandler S, Schnell A (1984) Long-term effects of cyclosporin A on cultured mouse pancreatic islets. Diabetologia 27(Suppl):66–69

    Article  CAS  PubMed  Google Scholar 

  • Antonioli B, Fermo I, Cainarca S, Marzorati S, Nano R, Baldissera M, Bachi A, Paroni R, Ricordi C, Bertuzzi F (2007) Characterization of collagenase blend enzymes for human islet transplantation. Transplantation 84(12):1568–1575

    Article  CAS  PubMed  Google Scholar 

  • Assady S, Maor G, Amit M, Itskovitz-Eldor J, Skorecki KL, Tzukerman M (2001) Insulin production by human embryonic stem cells. Diabetes 50(8):1691–1697

    Article  CAS  PubMed  Google Scholar 

  • Azevedo-Martins AK, Lortz S, Lenzen S, Curi R, Eizirik DL, Tiedge M (2003) Improvement of the mitochondrial antioxidant defense status prevents cytokine-induced nuclear factor-kappaB activation in insulin-producing cells. Diabetes 52(1):93–101

    Article  CAS  PubMed  Google Scholar 

  • Balamurugan AN, Chang Y, Bertera S, Sands A, Shankar V, Trucco M, Bottino R (2006) Suitability of human juvenile pancreatic islets for clinical use. Diabetologia 49(8):1845–1854

    Article  CAS  PubMed  Google Scholar 

  • Balamurugan AN, Breite AG, Anazawa T, Loganathan G, Wilhelm JJ, Papas KK, Dwulet FE, McCarthy RC, Hering BJ (2010) Successful human islet isolation and transplantation indicating the importance of class 1 collagenase and collagen degradation activity assay. Transplantation 89(8):954–961

    Article  CAS  PubMed  Google Scholar 

  • Balamurugan AN, Loganathan G, Bellin MD, Wilhelm JJ, Harmon J, Anazawa T, Soltani SM, Radosevich DM, Yuasa T, Tiwari M, Papas KK, McCarthy R, Sutherland DE, Hering BJ (2012) A new enzyme mixture to increase the yield and transplant rate of autologous and allogeneic human islet products. Transplantation 93(7):693–702

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Balamurugan AN, Loganathan G, Lockridge A, Soltani SM, Wilhelm JJ, Beilman GJ, Hering BJ, Sutherland DER (2014a) Islet of langerhans. Springer Reference, USA, pp. 1199–1227

    Google Scholar 

  • Balamurugan AN, Loganathan G, Lockridge A, Soltani SM, Wilhelm JJ, Beilman GJ, Hering BJ, Sutherland DER (2014b) Islet isolation from pancreatitis pancreas for autologous islet isolation. In: Islam MS (ed) Islet of langerhans, 2nd edn. vol. 1. Springer Reference, USA, pp. 1199–1227

    Google Scholar 

  • Balamurugan AN, Naziruddin B, Lockridge A, Tiwari M, Loganathan G, Takita M, Matsumoto S, Papas K, Trieger M, Rainis H, Kin T, Kay TW, Wease S, Messinger S, Ricordi C, Alejandro R, Markmann J, Kerr-Conti J, Rickels MR, Liu C, Zhang X, Witkowski P, Posselt A, Maffi P, Secchi A, Berney T, O’Connell PJ, Hering BJ, Barton FB (2014c) Islet product characteristics and factors related to successful human islet transplantation from the Collaborative Islet Transplant Registry (CITR) 1999–2010. Am J Transplant 14(11):2595–2606

    Google Scholar 

  • Balamurugan AN, Green M, Breite AG, Loganathan G, Wilhelm JJ, Tweed B, Vargova L, Lockridge A, Kuriti M, Hughes MG, Williams SK, Hering BJ, Dwulet F, McCarthy RC (2015) Identifying effective enzyme activity targets for recombinant class I and class II collagenase for successful human islet isolation. Transplant Direct 1:1199

    Google Scholar 

  • Banting FG, Best CH, Collip JB, Campbell WR, Fletcher AA (1922) Pancreatic extracts in the treatment of diabetes mellitus. Can Med Assoc J 12(3):141–146

    CAS  PubMed  PubMed Central  Google Scholar 

  • Barton FB, Rickels MR, Alejandro R, Hering BJ, Wease S, Naziruddin B, Oberholzer J, Odorico JS, Garfinkel MR, Levy M, Pattou F, Berney T, Secchi A, Messinger S, Senior PA, Maffi P, Posselt A, Stock PG, Kaufman DB, Luo X, Kandeel F, Cagliero E, Turgeon NA, Witkowski P, Naji A, O’Connell PJ, Greenbaum C, Kudva YC, Brayman KL, Aull MJ, Larsen C, Kay TW, Fernandez LA, Vantyghem MC, Bellin M, Shapiro AM (2012) Improvement in outcomes of clinical islet transplantation: 1999–2010. Diabetes Care 35(7):1436–1445

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bavister BD, Wolf DP, Brenner CA (2005) Challenges of primate embryonic stem cell research. Cloning Stem Cells 7(2):82–94

    Article  CAS  PubMed  Google Scholar 

  • Bellin MD, Barton FB, Heitman A, Harmon JV, Kandaswamy R, Balamurugan AN, Sutherland DE, Alejandro R, Hering BJ (2012) Potent induction immunotherapy promotes long-term insulin independence after islet transplantation in type 1 diabetes. Am J Transplant 12(6):1576–1583

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Berney T, Johnson PR (2010) Donor pancreata: evolving approaches to organ allocation for whole pancreas versus islet transplantation. Transplantation 90(3):238–243

    Article  PubMed  Google Scholar 

  • Berney T, Buhler LH, Morel P (2005) Pancreas allocation in the era of islet transplantation. Transpl Int 18(7):763–767

    Article  PubMed  Google Scholar 

  • Bertera S, Crawford ML, Alexander AM, Papworth GD, Watkins SC, Robbins PD, Trucco M (2003) Gene transfer of manganese superoxide dismutase extends islet graft function in a mouse model of autoimmune diabetes. Diabetes 52(2):387–393

    Article  CAS  PubMed  Google Scholar 

  • Blinman TA, Gukovsky I, Mouria M, Zaninovic V, Livingston E, Pandol SJ, Gukovskaya AS (2000) Activation of pancreatic acinar cells on isolation from tissue: cytokine upregulation via p38 MAP kinase. Am J Physiol Cell Physiol 279(6):C1993–C2003

    CAS  PubMed  Google Scholar 

  • Bonner-Weir S, Baxter LA, Schuppin GT, Smith FE (1993) A second pathway for regeneration of adult exocrine and endocrine pancreas. A possible recapitulation of embryonic development. Diabetes 42(12):1715–1720

    Article  CAS  PubMed  Google Scholar 

  • Bonner-Weir S, Toschi E, Inada A, Reitz P, Fonseca SY, Aye T, Sharma A (2004) The pancreatic ductal epithelium serves as a potential pool of progenitor cells. Pediatr Diabetes 5(Suppl 2):16–22

    Article  PubMed  Google Scholar 

  • Bottino R, Trucco M (2015) Clinical implementation of islet transplantation: a current assessment. Pediatr Diabetes 16(6):393–401

    Article  PubMed  Google Scholar 

  • Bottino R, Balamurugan AN, Bertera S, Pietropaolo M, Trucco M, Piganelli JD (2002a) Preservation of human islet cell functional mass by anti-oxidative action of a novel SOD mimic compound. Diabetes 51(8):2561–2567

    Article  CAS  PubMed  Google Scholar 

  • Bottino R, Balamurugan AN, Giannoukakis N, Trucco M (2002b) Islet/pancreas transplantation: challenges for pediatrics. Pediatr Diabetes 3(4):210–223

    Article  PubMed  Google Scholar 

  • Bottino R, Balamurugan AN, Tse H, Thirunavukkarasu C, Ge X, Profozich J, Milton M, Ziegenfuss A, Trucco M, Piganelli JD (2004) Response of human islets to isolation stress and the effect of antioxidant treatment. Diabetes 53(10):2559–2568

    Article  CAS  PubMed  Google Scholar 

  • Bottino R, Wijkstrom M, van der Windt DJ, Hara H, Ezzelarab M, Murase N, Bertera S, He J, Phelps C, Ayares D, Cooper DK, Trucco M (2014) Pig-to-monkey islet xenotransplantation using multi-transgenic pigs. Am J Transplant 14(10):2275–2287

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bouwens L, Pipeleers DG (1998) Extra-insular beta cells associated with ductules are frequent in adult human pancreas. Diabetologia 41(6):629–633

    Article  CAS  PubMed  Google Scholar 

  • Brown J, Matthews AL, Sandstrom PA, Chapman LE (1998) Xenotransplantation and the risk of retroviral zoonosis. Trends Microbiol 6(10):411–415

    Article  CAS  PubMed  Google Scholar 

  • Bruni A, Gala-Lopez B, Pepper AR, Abualhassan NS, Shapiro AJ (2014) Islet cell transplantation for the treatment of type 1 diabetes: recent advances and future challenges. Diabetes Metab Syndr Obes 7:211–223

    CAS  PubMed  PubMed Central  Google Scholar 

  • Cabric S, Sanchez J, Lundgren T, Foss A, Felldin M, Kallen R, Salmela K, Tibell A, Tufveson G, Larsson R, Korsgren O, Nilsson B (2007) Islet surface heparinization prevents the instant blood-mediated inflammatory reaction in islet transplantation. Diabetes 56(8):2008–2015

    Article  CAS  PubMed  Google Scholar 

  • Calne RY, Rolles K, White DJ, Thiru S, Evans DB, McMaster P, Dunn DC, Craddock GN, Henderson RG, Aziz S, Lewis P (1979) Cyclosporin A initially as the only immunosuppressant in 34 recipients of cadaveric organs: 32 kidneys, 2 pancreases, and 2 livers. Lancet 2(8151):1033–1036

    Article  CAS  PubMed  Google Scholar 

  • Cardona K, Korbutt GS, Milas Z, Lyon J, Cano J, Jiang W, Bello-Laborn H, Hacquoil B, Strobert E, Gangappa S, Weber CJ, Pearson TC, Rajotte RV, Larsen CP (2006) Long-term survival of neonatal porcine islets in nonhuman primates by targeting costimulation pathways. Nat Med 12(3):304–306

    Article  CAS  PubMed  Google Scholar 

  • Carroll PB, Ricordi C, Rilo HR, Fontes P, Khan R, Tzakis AG, Shapiro R, Fung JJ, Starzl TE (1992) Intrahepatic human islet transplantation at the University of Pittsburgh: results in 25 consecutive cases. Transplant Proc 24(6):3038–3039

    CAS  PubMed  PubMed Central  Google Scholar 

  • Centers for American Diabetes Association (2014) Statistics about diabetes. Data from the National Diabetes Statistics Report, 2014 (released June 10, 2014). http://www.diabetes.org/diabetes-basics/statistics/. Last accessed Feb 2016

  • Clinical Islet Transplant Study (2014) https://www.isletstudy.org/

  • Cooper DK, Casu A (2009) The International Xenotransplantation Association consensus statement on conditions for undertaking clinical trials of porcine islet products in type 1 diabetes – chapter 4: pre-clinical efficacy and complication data required to justify a clinical trial. Xenotransplantation 16(4):229–238

    Article  PubMed  Google Scholar 

  • Cryer PE (2005) Mechanisms of hypoglycemia-associated autonomic failure and its component syndromes in diabetes. Diabetes 54(12):3592–3601

    Article  CAS  PubMed  Google Scholar 

  • Disease Control and Prevention (2014) National Diabetes Statistics Report. http://www.cdc.gov/diabetes/data/statistics/2014statisticsreport.html. Last accessed Feb 2016

  • Elliott RB, Escobar L, Tan PL, Muzina M, Zwain S, Buchanan C (2007) Live encapsulated porcine islets from a type 1 diabetic patient 9.5 yr after xenotransplantation. Xenotransplantation 14(2):157–161

    Article  PubMed  Google Scholar 

  • Evans JL, Goldfine ID, Maddux BA, Grodsky GM (2003) Are oxidative stress-activated signaling pathways mediators of insulin resistance and beta-cell dysfunction? Diabetes 52(1):1–8

    Article  CAS  PubMed  Google Scholar 

  • Fahrmann ER, Adkins L, Loader CJ, Han H, Rice KM, Denvir J, Driscoll HK (2015) Severe hypoglycemia and coronary artery calcification during the diabetes control and complications trial/epidemiology of diabetes interventions and complications (DCCT/EDIC) study. Diabetes Res Clin Pract 107(2):280–289

    Article  CAS  PubMed  Google Scholar 

  • Farney AC, Xenos E, Sutherland DE, Widmer M, Stephanian E, Field MJ, Kaufman DB, Stevens RB, Blazar B, Platt J et al (1993) Inhibition of pancreatic islet beta cell function by tumor necrosis factor is blocked by a soluble tumor necrosis factor receptor. Transplant Proc 25(1 Pt 2):865–866

    CAS  PubMed  Google Scholar 

  • Froud T, Ricordi C, Baidal DA, Hafiz MM, Ponte G, Cure P, Pileggi A, Poggioli R, Ichii H, Khan A, Ferreira JV, Pugliese A, Esquenazi VV, Kenyon NS, Alejandro R (2005) Islet transplantation in type 1 diabetes mellitus using cultured islets and steroid-free immunosuppression: Miami experience. Am J Transplant 5(8):2037–2046

    Article  PubMed  Google Scholar 

  • Fujino Y (2010) Two-layer cold storage method for pancreas and islet cell transplantation. World J Gastroenterol 16(26):3235–3238

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gangemi A, Salehi P, Hatipoglu B, Martellotto J, Barbaro B, Kuechle JB, Qi M, Wang Y, Pallan P, Owens C, Bui J, West D, Kaplan B, Benedetti E, Oberholzer J (2008) Islet transplantation for brittle type 1 diabetes: the UIC protocol. Am J Transplant 8(6):1250–1261

    Article  CAS  PubMed  Google Scholar 

  • Giannoukakis N, Rudert WA, Trucco M, Robbins PD (2000) Protection of human islets from the effects of interleukin-1beta by adenoviral gene transfer of an Ikappa B repressor. J Biol Chem 275(47):36509–36513

    Article  CAS  PubMed  Google Scholar 

  • Groth CG, Korsgren O, Tibell A, Tollemar J, Moller E, Bolinder J, Ostman J, Reinholt FP, Hellerstrom C, Andersson A (1994) Transplantation of porcine fetal pancreas to diabetic patients. Lancet 344(8934):1402–1404

    Article  CAS  PubMed  Google Scholar 

  • Guibert EE, Petrenko AY, Balaban CL, Somov AY, Rodriguez JV, Fuller BJ (2011) Organ preservation: current concepts and new strategies for the next decade. Transfus Med Hemother 38(2):125–142

    Article  PubMed  PubMed Central  Google Scholar 

  • Hawthorne WJ, Salvaris EJ, Phillips P, Hawkes J, Liuwantara D, Burns H, Barlow H, Stewart AB, Peirce SB, Hu M, Lew AM, Robson SC, Nottle MB, D’Apice AJ, O’Connell PJ, Cowan PJ (2014) Control of IBMIR in neonatal porcine islet xenotransplantation in baboons. Am J Transplant 14(6):1300–1309

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hering BJ, Matsumoto I, Sawada T, Nakano M, Sakai T, Kandaswamy R, Sutherland DE (2002) Impact of two-layer pancreas preservation on islet isolation and transplantation. Transplantation 74(12):1813–1816

    Article  PubMed  Google Scholar 

  • Hering BJ, Kandaswamy R, Ansite JD, Eckman PM, Nakano M, Sawada T, Matsumoto I, Ihm SH, Zhang HJ, Parkey J, Hunter DW, Sutherland DE (2005) Single-donor, marginal-dose islet transplantation in patients with type 1 diabetes. JAMA 293(7):830–835

    Article  CAS  PubMed  Google Scholar 

  • Hering BJ, Wijkstrom M, Graham ML, Hardstedt M, Aasheim TC, Jie T, Ansite JD, Nakano M, Cheng J, Li W, Moran K, Christians U, Finnegan C, Mills CD, Sutherland DE, Bansal-Pakala P, Murtaugh MP, Kirchhof N, Schuurman HJ (2006) Prolonged diabetes reversal after intraportal xenotransplantation of wild-type porcine islets in immunosuppressed nonhuman primates. Nat Med 12(3):301–303

    Article  CAS  PubMed  Google Scholar 

  • Hering BJ, Cooper DK, Cozzi E, Schuurman HJ, Korbutt GS, Denner J, O’Connell PJ, Vanderpool HY, Pierson RN 3rd (2009) The International Xenotransplantation Association consensus statement on conditions for undertaking clinical trials of porcine islet products in type 1 diabetes – executive summary. Xenotransplantation 16(4):196–202

    Article  PubMed  Google Scholar 

  • Hoeldtke RD, Bryner KD, McNeill DR, Warehime SS, Van Dyke K, Hobbs G (2003) Oxidative stress and insulin requirements in patients with recent-onset type 1 diabetes. J Clin Endocrinol Metab 88(4):1624–1628

    Article  CAS  PubMed  Google Scholar 

  • Hoeldtke RD, Bryner KD, VanDyke K (2011) Oxidative stress and autonomic nerve function in early type 1 diabetes. Clin Auton Res 21(1):19–28

    Article  PubMed  Google Scholar 

  • Hua XF, Wang YW, Tang YX, Yu SQ, Jin SH, Meng XM, Li HF, Liu FJ, Sun Q, Wang HY, Li JY (2014) Pancreatic insulin-producing cells differentiated from human embryonic stem cells correct hyperglycemia in SCID/NOD mice, an animal model of diabetes. PLoS One 9(7):e102198

    Article  PubMed  PubMed Central  Google Scholar 

  • Ichii H, Ricordi C (2009) Current status of islet cell transplantation. J Hepatobiliary Pancreat Surg 16(2):101–112

    Article  PubMed  Google Scholar 

  • Jiang R, Han Z, Zhuo G, Qu X, Li X, Wang X, Shao Y, Yang S, Han ZC (2011) Transplantation of placenta-derived mesenchymal stem cells in type 2 diabetes: a pilot study. Front Med 5(1):94–100

    Article  PubMed  Google Scholar 

  • Jun HS (2010) Cell replacement and regeneration therapy for diabetes. Korean Diabetes J 34(2):77–83

    Article  PubMed  PubMed Central  Google Scholar 

  • Kandaswamy R, Sutherland DE (2006) Pancreas versus islet transplantation in diabetes mellitus: how to allocate deceased donor pancreata? Transplant Proc 38(2):365–367

    Article  CAS  PubMed  Google Scholar 

  • Kourtzelis I, Magnusson PU, Kotlabova K, Lambris JD, Chavakis T (2015) Regulation of instant blood mediated inflammatory reaction (IBMIR) in pancreatic islet xeno-transplantation: points for therapeutic interventions. Adv Exp Med Biol 865:171–188

    Article  PubMed  Google Scholar 

  • Lacy PE, Kostianovsky M (1967) Method for the isolation of intact islets of Langerhans from the rat pancreas. Diabetes 16(1):35–39

    Article  CAS  PubMed  Google Scholar 

  • Lakey JR, Warnock GL, Shapiro AM, Korbutt GS, Ao Z, Kneteman NM, Rajotte RV (1999) Intraductal collagenase delivery into the human pancreas using syringe loading or controlled perfusion. Cell Transplant 8(3):285–292

    CAS  PubMed  Google Scholar 

  • Lakey JR, Kneteman NM, Rajotte RV, Wu DC, Bigam D, Shapiro AM (2002) Effect of core pancreas temperature during cadaveric procurement on human islet isolation and functional viability. Transplantation 73(7):1106–1110

    Article  PubMed  Google Scholar 

  • Lakey JR, Burridge PW, Shapiro AM (2003) Technical aspects of islet preparation and transplantation. Transpl Int 16(9):613–632

    Article  PubMed  Google Scholar 

  • Linetsky E, Ricordi C (2008) Regulatory challenges in manufacturing of pancreatic islets. Transplant Proc 40(2):424–426

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Linetsky E, Bottino R, Lehmann R, Alejandro R, Inverardi L, Ricordi C (1997a) Improved human islet isolation using a new enzyme blend, liberase. Diabetes 46(7):1120–1123

    Article  CAS  PubMed  Google Scholar 

  • Linetsky E, Lehmann R, Li H, Fernandez L, Bottino R, Selvaggi G, Alejandro R, Ricordi C (1997b) Human islet isolation using a new enzyme blend. Transplant Proc 29(4):1957–1958

    Article  CAS  PubMed  Google Scholar 

  • Loganathan G, Dawra RK, Pugazhenthi S, Guo Z, Soltani SM, Wiseman A, Sanders MA, Papas KK, Velayutham K, Saluja AK, Sutherland DE, Hering BJ, Balamurugan AN (2011) Insulin degradation by acinar cell proteases creates a dysfunctional environment for human islets before/after transplantation: benefits of alpha-1 antitrypsin treatment. Transplantation 92(11):1222–1230

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Maffi P, Bertuzzi F, De Taddeo F, Magistretti P, Nano R, Fiorina P, Caumo A, Pozzi P, Socci C, Venturini M, del Maschio A, Secchi A (2007) Kidney function after islet transplant alone in type 1 diabetes: impact of immunosuppressive therapy on progression of diabetic nephropathy. Diabetes Care 30(5):1150–1155

    Article  CAS  PubMed  Google Scholar 

  • Markmann JF, Deng S, Huang X, Desai NM, Velidedeoglu EH, Lui C, Frank A, Markmann E, Palanjian M, Brayman K, Wolf B, Bell E, Vitamaniuk M, Doliba N, Matschinsky F, Barker CF, Naji A (2003) Insulin independence following isolated islet transplantation and single islet infusions. Ann Surg 237(6):741–749; discussion 749–750

    PubMed  PubMed Central  Google Scholar 

  • Matsumoto S (2005) Clinical application of perfluorocarbons for organ preservation. Artif Cells Blood Substit Immobil Biotechnol 33(1):75–82

    Article  CAS  PubMed  Google Scholar 

  • Matsumoto S (2011) Clinical allogeneic and autologous islet cell transplantation: update. Diabetes Metab J 35(3):199–206

    Article  PubMed  PubMed Central  Google Scholar 

  • McCall M, Shapiro AM (2014) Islet cell transplantation. Semin Pediatr Surg 23(2):83–90

    Article  PubMed  Google Scholar 

  • Members of the islet manufacturing NIH-CIT consortium (2014a) The NIH CIT consortium: purified human pancreatic islets (PHPI) master production batch record – a standard operating procedure of the NIH clinical islet transplantation consortium. http://www.cellr4.org/article/891. Last accessed Feb 2016. CellR4 1(1)

  • Members of the islet manufacturing NIH-CIT consortium (2014b) The NIH CIT consortium: standard methods and operating procedures. http://www.cellr4.org/article/891. Last accessed Feb 2016. CellR4 1(1)

  • Minami K, Okuno M, Miyawaki K, Okumachi A, Ishizaki K, Oyama K, Kawaguchi M, Ishizuka N, Iwanaga T, Seino S (2005) Lineage tracing and characterization of insulin-secreting cells generated from adult pancreatic acinar cells. Proc Natl Acad Sci U S A 102(42):15116–15121

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mullon C (1999) Bioartificial organs may help reduce risk of zoonosis in xenotransplantation. Artif Organs 23(4):366–367

    Article  CAS  PubMed  Google Scholar 

  • Najarian JS, Sutherland DE, Matas AJ, Steffes MW, Simmons RL, Goetz FC (1977) Human islet transplantation: a preliminary report. Transplant Proc 9(1):233–236

    CAS  PubMed  Google Scholar 

  • Naziruddin B, Iwahashi S, Kanak MA, Takita M, Itoh T, Levy MF (2014) Evidence for instant blood-mediated inflammatory reaction in clinical autologous islet transplantation. Am J Transplant 14(2):428–437

    Article  CAS  PubMed  Google Scholar 

  • Nielsen JH, Mandruppoulsen T, Nerup J (1986) Direct effects of cyclosporine-a on human pancreatic beta-cells. Diabetes 35(9):1049–1052

    Article  CAS  PubMed  Google Scholar 

  • Noguchi H (2011) Pancreas procurement and preservation for islet transplantation: personal considerations. J Transplant 2011:783168

    Article  PubMed  PubMed Central  Google Scholar 

  • Oberholzer J, Shapiro AM, Lakey JR, Ryan EA, Rajotte RV, Korbutt GS, Morel P, Kneteman NM (2003) Current status of islet cell transplantation. Adv Surg 37:253–282

    PubMed  Google Scholar 

  • Onkamo P, Vaananen S, Karvonen M, Tuomilehto J (1999) Worldwide increase in incidence of type I diabetes – the analysis of the data on published incidence trends. Diabetologia 42(12):1395–1403

    Article  CAS  PubMed  Google Scholar 

  • Pan FC, Wright C (2011) Pancreas organogenesis: from bud to plexus to gland. Dev Dyn 240(3):530–565

    Article  CAS  PubMed  Google Scholar 

  • Panero F, Novelli G, Zucco C, Fornengo P, Perotto M, Segre O, Grassi G, Cavallo-Perin P, Bruno G (2009) Fasting plasma C-peptide and micro- and macrovascular complications in a large clinic-based cohort of type 1 diabetic patients. Diabetes Care 32(2):301–305

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Papas KK, Suszynski TM, Colton CK (2009) Islet assessment for transplantation. Curr Opin Organ Transplant 14(6):674–682

    Article  PubMed  PubMed Central  Google Scholar 

  • Paraskevas S, Maysinger D, Wang R, Duguid TP, Rosenberg L (2000) Cell loss in isolated human islets occurs by apoptosis. Pancreas 20(3):270–276

    Article  CAS  PubMed  Google Scholar 

  • Patience C, Takeuchi Y, Weiss RA (1998) Zoonosis in xenotransplantation. Curr Opin Immunol 10(5):539–542

    Article  CAS  PubMed  Google Scholar 

  • Pedersen-Bjergaard U, Pramming S, Heller SR, Wallace TM, Rasmussen AK, Jorgensen HV, Matthews DR, Hougaard P, Thorsteinsson B (2004) Severe hypoglycaemia in 1076 adult patients with type 1 diabetes: influence of risk markers and selection. Diabetes Metab Res Rev 20(6):479–486

    Article  PubMed  Google Scholar 

  • Pepper AR, Gala-Lopez B, Ziff O, Shapiro AJ (2013) Current status of clinical islet transplantation. World J Transplant 3(4):48–53

    PubMed  PubMed Central  Google Scholar 

  • Phadnis SM, Ghaskadbi SM, Hardikar AA, Bhonde RR (2009) Mesenchymal stem cells derived from bone marrow of diabetic patients portrait unique markers influenced by the diabetic microenvironment. Rev Diabet Stud 6(4):260–270

    Article  PubMed  Google Scholar 

  • Pileggi A, Molano RD, Berney T, Cattan P, Vizzardelli C, Oliver R, Fraker C, Ricordi C, Pastori RL, Bach FH, Inverardi L (2001) Heme oxygenase-1 induction in islet cells results in protection from apoptosis and improved in vivo function after transplantation. Diabetes 50(9):1983–1991

    Article  CAS  PubMed  Google Scholar 

  • Platt JL (2000) Zoonosis in xenotransplantation. Transplant Proc 32(7):1551

    Article  CAS  PubMed  Google Scholar 

  • Polonsky KS (2012) The past 200 years in diabetes. N Engl J Med 367(14):1332–1340

    Article  CAS  PubMed  Google Scholar 

  • Posselt AM, Bellin MD, Tavakol M, Szot GL, Frassetto LA, Masharani U, Kerlan RK, Fong L, Vincenti FG, Hering BJ, Bluestone JA, Stock PG (2010) Islet transplantation in type 1 diabetics using an immunosuppressive protocol based on the anti-LFA-1 antibody efalizumab. Am J Transplant 10(8):1870–1880

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Quan N, Ho E, La W, Tsai YH, Bray T (2001) Administration of NF-kappaB decoy inhibits pancreatic activation of NF-kappaB and prevents diabetogenesis by alloxan in mice. FASEB J 15(9):1616–1618

    CAS  PubMed  Google Scholar 

  • Rao GM, Morghom LO (1990) Secondary diabetic complications and biochemical parameters. Indian J Med Sci 44(11):299–303

    CAS  PubMed  Google Scholar 

  • Redfield RR, Scalea JR, Odorico JS (2015) Simultaneous pancreas and kidney transplantation: current trends and future directions. Curr Opin Organ Transplant 20(1):94–102

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rescan C, Le Bras S, Lefebvre VH, Frandsen U, Klein T, Foschi M, Pipeleers DG, Scharfmann R, Madsen OD, Heimberg H (2005) EGF-induced proliferation of adult human pancreatic duct cells is mediated by the MEK/ERK cascade. Lab Invest 85(1):65–74

    Article  CAS  PubMed  Google Scholar 

  • Ricordi C, Lacy PE, Finke EH, Olack BJ, Scharp DW (1988) Automated method for isolation of human pancreatic islets. Diabetes 37(4):413–420

    Article  CAS  PubMed  Google Scholar 

  • Ricordi C, Fraker C, Szust J, Al-Abdullah I, Poggioli R, Kirlew T, Khan A, Alejandro R (2003) Improved human islet isolation outcome from marginal donors following addition of oxygenated perfluorocarbon to the cold-storage solution. Transplantation 75(9):1524–1527

    Article  PubMed  Google Scholar 

  • Robertson RP (1986) Cyclosporin-induced inhibition of insulin secretion in isolated rat islets and HIT cells. Diabetes 35(9):1016–1019

    Article  CAS  PubMed  Google Scholar 

  • Robertson RP, Harmon J, Tran PO, Tanaka Y, Takahashi H (2003) Glucose toxicity in beta-cells: type 2 diabetes, good radicals gone bad, and the glutathione connection. Diabetes 52(3):581–587

    Article  CAS  PubMed  Google Scholar 

  • Rovira M, Scott SG, Liss AS, Jensen J, Thayer SP, Leach SD (2010) Isolation and characterization of centroacinar/terminal ductal progenitor cells in adult mouse pancreas. Proc Natl Acad Sci U S A 107(1):75–80

    Article  CAS  PubMed  Google Scholar 

  • Ryan EA, Paty BW, Senior PA, Bigam D, Alfadhli E, Kneteman NM, Lakey JR, Shapiro AM (2005) Five-year follow-up after clinical islet transplantation. Diabetes 54(7):2060–2069

    Article  CAS  PubMed  Google Scholar 

  • Sa JR, Gonzalez AM, Melaragno CS, Saitovich D, Franco DR, Rangel EB, Noronha IL, Pestana JO, Bertoluci MC, Linhares M, Miranda MP, Monteagudo P, Genzini T, Eliaschewitz FG (2008) Pancreas and islet transplantation in patients with diabetes mellitus. Arq Bras Endocrinol Metabol 52(2):355–366

    Article  PubMed  Google Scholar 

  • Sapir T, Shternhall K, Meivar-Levy I, Blumenfeld T, Cohen H, Skutelsky E, Eventov-Friedman S, Barshack I, Goldberg I, Pri-Chen S, Ben-Dor L, Polak-Charcon S, Karasik A, Shimon I, Mor E, Ferber S (2005) Cell-replacement therapy for diabetes: generating functional insulin-producing tissue from adult human liver cells. Proc Natl Acad Sci U S A 102(22):7964–7969

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schuurman HJ (2009) The International Xenotransplantation Association consensus statement on conditions for undertaking clinical trials of porcine islet products in type 1 diabetes – chapter 2: source pigs. Xenotransplantation 16(4):215–222

    Article  PubMed  Google Scholar 

  • Schuurman HJ (2015) Regulatory aspects of clinical xenotransplantation. Int J Surg 23(Pt B):312–321

    Google Scholar 

  • Shapiro AM, Lakey JR, Ryan EA, Korbutt GS, Toth E, Warnock GL, Kneteman NM, Rajotte RV (2000) Islet transplantation in seven patients with type 1 diabetes mellitus using a glucocorticoid-free immunosuppressive regimen. N Engl J Med 343(4):230–238

    Article  CAS  PubMed  Google Scholar 

  • Shapiro AM, Lakey JR, Paty BW, Senior PA, Bigam DL, Ryan EA (2005) Strategic opportunities in clinical islet transplantation. Transplantation 79(10):1304–1307

    Article  PubMed  Google Scholar 

  • Shapiro AM, Ricordi C, Hering BJ, Auchincloss H, Lindblad R, Robertson RP, Secchi A, Brendel MD, Berney T, Brennan DC, Cagliero E, Alejandro R, Ryan EA, DiMercurio B, Morel P, Polonsky KS, Reems JA, Bretzel RG, Bertuzzi F, Froud T, Kandaswamy R, Sutherland DE, Eisenbarth G, Segal M, Preiksaitis J, Korbutt GS, Barton FB, Viviano L, Seyfert-Margolis V, Bluestone J, Lakey JR (2006) International trial of the Edmonton protocol for islet transplantation. N Engl J Med 355(13):1318–1330

    Article  CAS  PubMed  Google Scholar 

  • Shi Y (2010) Generation of functional insulin-producing cells from human embryonic stem cells in vitro. Methods Mol Biol 636:79–85

    Article  PubMed  Google Scholar 

  • Shibata S, Matsumoto S, Sageshima J, Hiraoka K, Sutherland DE, Kirchhof N, Guo Z, Koyama K, Gilmore TR, Dunning M, Ansite JD, Shearer JD, Clemmings S, Hedlund BE, Sehgal SN, Hering BJ (2001) Temporary treatment with sirolimus and low-trough cyclosporine prevents acute islet allograft rejection, and combination with starch-conjugated deferoxamine promotes islet engraftment in the preclinical pig model. Transplant Proc 33(1–2):509

    Article  CAS  PubMed  Google Scholar 

  • Shin JS, Kim JM, Kim JS, Min BH, Kim YH, Kim HJ, Jang JY, Yoon IH, Kang HJ, Kim J, Hwang ES, Lim DG, Lee WW, Ha J, Jung KC, Park SH, Kim SJ, Park CG (2015) Long-term control of diabetes in immunosuppressed nonhuman primates (NHP) by the transplantation of adult porcine islets. Am J Transplant 15(11):2837–2850

    Article  CAS  PubMed  Google Scholar 

  • Sutherland DE (2003) Current status of beta-cell replacement therapy (pancreas and islet transplantation) for treatment of diabetes mellitus. Transplant Proc 35(5):1625–1627

    Article  CAS  PubMed  Google Scholar 

  • Sutherland DE, Gruessner A, Hering BJ (2004) Beta-cell replacement therapy (pancreas and islet transplantation) for treatment of diabetes mellitus: an integrated approach. Endocrinol Metab Clin North Am 33(1):135–148, x

    Article  PubMed  Google Scholar 

  • Swales N, Martens GA, Bonne S, Heremans Y, Borup R, Van de Casteele M, Ling Z, Pipeleers D, Ravassard P, Nielsen F, Ferrer J, Heimberg H (2012) Plasticity of adult human pancreatic duct cells by neurogenin3-mediated reprogramming. PLoS One 7(5), e37055

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tanaka T, Suzuki Y, Tanioka Y, Sakai T, Kakinoki K, Goto T, Li S, Yoshikawa T, Matsumoto I, Fujino Y, Kuroda Y (2005) Possibility of islet transplantation from a nonheartbeating donor pancreas resuscitated by the two-layer method. Transplantation 80(6):738–742

    Article  PubMed  Google Scholar 

  • The diabetes control and complications trial research group (1993) The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. The Diabetes Control and Complications Trial Research Group. N Engl J Med 329(14): 977–986

    Google Scholar 

  • The diabetes control and complications trial research group (1994) Effect of intensive diabetes treatment on the development and progression of long-term complications in adolescents with insulin-dependent diabetes mellitus: Diabetes Control and Complications Trial. Diabetes Control and Complications Trial Research Group. J Pediatr 125(2): 177–188

    Google Scholar 

  • Thompson DM, Begg IS, Harris C, Ao Z, Fung MA, Meloche RM, Keown P, Meneilly GS, Shapiro RJ, Ho S, Dawson KG, Al Ghofaili K, Al Riyami L, Al Mehthel M, Kozak SE, Tong SO, Warnock GL (2008) Reduced progression of diabetic retinopathy after islet cell transplantation compared with intensive medical therapy. Transplantation 85(10):1400–1405

    Article  PubMed  Google Scholar 

  • Thompson DM, Meloche M, Ao Z, Paty B, Keown P, Shapiro RJ, Ho S, Worsley D, Fung M, Meneilly G, Begg I, Al Mehthel M, Kondi J, Harris C, Fensom B, Kozak SE, Tong SO, Trinh M, Warnock GL (2011a) Reduced progression of diabetic microvascular complications with islet cell transplantation compared with intensive medical therapy. Transplantation 91(3):373–378

    Article  PubMed  Google Scholar 

  • Thompson P, Badell IR, Lowe M, Cano J, Song M, Leopardi F, Avila J, Ruhil R, Strobert E, Korbutt G, Rayat G, Rajotte R, Iwakoshi N, Larsen CP, Kirk AD (2011b) Islet xenotransplantation using gal-deficient neonatal donors improves engraftment and function. Am J Transplant 11(12):2593–2602

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Thorel F, Nepote V, Avril I, Kohno K, Desgraz R, Chera S, Herrera PL (2010) Conversion of adult pancreatic alpha-cells to beta-cells after extreme beta-cell loss. Nature 464(7292):1149–1154

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Trivedi HL, Vanikar AV, Thakker U, Firoze A, Dave SD, Patel CN, Patel JV, Bhargava AB, Shankar V (2008) Human adipose tissue-derived mesenchymal stem cells combined with hematopoietic stem cell transplantation synthesize insulin. Transplant Proc 40(4):1135–1139

    Article  CAS  PubMed  Google Scholar 

  • Tsujimura T, Kuroda Y, Kin T, Avila JG, Rajotte RV, Korbutt GS, Ryan EA, Shapiro AM, Lakey JR (2002) Human islet transplantation from pancreases with prolonged cold ischemia using additional preservation by the two-layer (UW solution/perfluorochemical) cold-storage method. Transplantation 74(12):1687–1691

    Article  CAS  PubMed  Google Scholar 

  • Tsujimura T, Kuroda Y, Avila JG, Kin T, Churchill TA, Shapiro AM, Lakey JR (2003) Resuscitation of the ischemically damaged human pancreas by the two-layer method prior to islet isolation. Transplant Proc 35(7):2461–2462

    Article  CAS  PubMed  Google Scholar 

  • Turgeon NA, Avila JG, Cano JA, Hutchinson JJ, Badell IR, Page AJ, Adams AB, Sears MH, Bowen PH, Kirk AD, Pearson TC, Larsen CP (2010) Experience with a novel efalizumab-based immunosuppressive regimen to facilitate single donor islet cell transplantation. Am J Transplant 10(9):2082–2091

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • UK prospective diabetes study (UKPDS 33) group (1998) Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group. Lancet 352(9131): 837–853

    Google Scholar 

  • Valdes-Gonzalez RA, Dorantes LM, Garibay GN, Bracho-Blanchet E, Mendez AJ, Davila-Perez R, Elliott RB, Teran L, White DJ (2005) Xenotransplantation of porcine neonatal islets of Langerhans and Sertoli cells: a 4-year study. Eur J Endocrinol 153(3):419–427

    Article  CAS  PubMed  Google Scholar 

  • Van Belle T, von Herrath M (2008) Immunosuppression in islet transplantation. J Clin Invest 118(5):1625–1628

    PubMed  PubMed Central  Google Scholar 

  • van der Windt DJ, Bottino R, Casu A, Campanile N, Smetanka C, He J, Murase N, Hara H, Ball S, Loveland BE, Ayares D, Lakkis FG, Cooper DK, Trucco M (2009) Long-term controlled normoglycemia in diabetic non-human primates after transplantation with hCD46 transgenic porcine islets. Am J Transplant 9(12):2716–2726

    Article  PubMed  CAS  Google Scholar 

  • Vasudevan AR, Burns A, Fonseca VA (2006) The effectiveness of intensive glycemic control for the prevention of vascular complications in diabetes mellitus. Treat Endocrinol 5(5):273–286

    Article  CAS  PubMed  Google Scholar 

  • Vierbuchen T, Wernig M (2011) Direct lineage conversions: unnatural but useful? Nat Biotechnol 29(10):892–907

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vrochides D, Paraskevas S, Papanikolaou V (2009) Transplantation for type 1 diabetes mellitus. Whole organ or islets? Hippokratia 13(1):6–8

    CAS  PubMed  PubMed Central  Google Scholar 

  • Wang W, Mo Z, Ye B, Hu P, Liu S, Yi S (2011) A clinical trial of xenotransplantation of neonatal pig islets for diabetic patients. Zhong Nan Da Xue Xue Bao Yi Xue Ban 36(12):1134–1140

    CAS  PubMed  Google Scholar 

  • Wild S, Roglic G, Green A, Sicree R, King H (2004) Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care 27(5):1047–1053

    Article  PubMed  Google Scholar 

  • Yakimets WJ, Lakey JR, Yatscoff RW, Katyal D, Ao Z, Finegood DT, Rajotte RV, Kneteman NM (1993) Prolongation of canine pancreatic islet allograft survival with combined rapamycin and cyclosporine therapy at low doses. Rapamycin efficacy is blood level related. Transplantation 56(6):1293–1298

    Article  CAS  PubMed  Google Scholar 

  • Yang Y, Akinci E, Dutton JR, Banga A, Slack JM (2013) Stage specific reprogramming of mouse embryo liver cells to a beta cell-like phenotype. Mech Dev 130(11–12):602–612

    Article  CAS  PubMed  Google Scholar 

  • Yoshimura N, Matsui S, Hamashima T, Oka T (1989) Effect of a new immunosuppressive agent, FK506, on human lymphocyte responses in vitro. II. Inhibition of the production of IL-2 and gamma-IFN, but not B cell-stimulating factor 2. Transplantation 47(2):356–359

    Article  CAS  PubMed  Google Scholar 

  • Zeyland J, Gawronska B, Juzwa W, Jura J, Nowak A, Slomski R, Smorag Z, Szalata M, Wozniak A, Lipinski D (2013) Transgenic pigs designed to express human alpha-galactosidase to avoid humoral xenograft rejection. J Appl Genet 54(3):293–303

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhou Q, Brown J, Kanarek A, Rajagopal J, Melton DA (2008) In vivo reprogramming of adult pancreatic exocrine cells to beta-cells. Nature 455(7213):627–632

    Article  CAS  PubMed  Google Scholar 

  • Zhu HT, Wang WL, Yu L, Wang B (2014) Pig-islet xenotransplantation: recent progress and current perspectives. Front Surg 1:7

    Article  PubMed  PubMed Central  Google Scholar 

  • Zsom L, Wagner L, Fulop T (2015) Minimization vs tailoring: where do we stand with personalized immunosuppression during renal transplantation in 2015? World J Transplant 5(3):73–80

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgment

The authors thank the Jewish Heritage Fund for Excellence for providing generous support to initiate islet transplantation program at the University of Louisville. The authors thank Kentucky Organ Donor Affiliates (KODA) for the supply of human pancreases to our program. Special thanks to Leigh Kleinert, B. Vishaal, and Agharnan Gandhi for providing valuable comments.

Author information

Authors and Affiliations

  1. Clinical Islet Cell Laboratory, Department of Surgery, Cardiovascular Innovation Institute, University of Louisville, Louisville, KY, 40202, USA

    Appakalai N. Balamurugan, Gopalakrishnan Loganathan, Benjamin Tweed, William W. Tucker & Michael G. Hughes

  2. School of Biosciences and Technology, VIT University, Vellore, 632014, TN, India

    Venugopal Subhashree

  3. Bioficial Organs Program, Cardiovascular Innovation Institute, University of Louisville, Louisville, KY, 40202, USA

    Stuart K. Williams

  4. Department of Endocrinology, University of Louisville, Louisville, KY, USA

    Sri Prakash L. Mokshagundam

Authors
  1. Appakalai N. Balamurugan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Gopalakrishnan Loganathan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Benjamin Tweed
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. William W. Tucker
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Venugopal Subhashree
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Sri Prakash L. Mokshagundam
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Michael G. Hughes
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Stuart K. Williams
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Appakalai N. Balamurugan .

Editor information

Editors and Affiliations

  1. Organ Transplantation, Hackensack University Medical Center Transplant Surgery and, Hackensack, New Jersey, USA

    James W. Lim

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer International Publishing AG

About this entry

Cite this entry

Balamurugan, A.N. et al. (2016). Islet Cell Transplant. In: Lim, J. (eds) Contemporary Pancreas Transplantation. Organ and Tissue Transplantation. Springer, Cham. https://doi.org/10.1007/978-3-319-20789-6_9-2

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-20789-6_9-2

  • Received:

  • Accepted:

  • Published:

  • Publisher Name: Springer, Cham

  • Online ISBN: 978-3-319-20789-6

  • eBook Packages: Springer Reference MedicineReference Module Medicine

Publish with us

Policies and ethics

Chapter history

  1. Latest

    Islet Cell Transplant
    Published:
    10 December 2016

    DOI: https://doi.org/10.1007/978-3-319-20789-6_9-2

  2. Original

    Islet Cell Transplant
    Published:
    11 May 2016

    DOI: https://doi.org/10.1007/978-3-319-20789-6_9-1

Search

Navigation