Acta Diabetologica

, Volume 53, Issue 5, pp 683–691 | Cite as

The state of the art of islet transplantation and cell therapy in type 1 diabetes

  • Silvia Pellegrini
  • Elisa Cantarelli
  • Valeria Sordi
  • Rita Nano
  • Lorenzo Piemonti
Review Article


In patients with type 1 diabetes (T1D), pancreatic β cells are destroyed by a selective autoimmune attack and their replacement with functional insulin-producing cells is the only possible cure for this disease. The field of islet transplantation has evolved significantly from the breakthrough of the Edmonton Protocol in 2000, since significant advances in islet isolation and engraftment, together with improved immunosuppressive strategies, have been reported. The main limitations, however, remain the insufficient supply of human tissue and the need for lifelong immunosuppression therapy. Great effort is then invested in finding innovative sources of insulin-producing β cells. One old alternative with new recent perspectives is the use of non-human donor cells, in particular porcine β cells. Also the field of preexisting β cell expansion has advanced, with the development of new human β cell lines. Yet, large-scale production of human insulin-producing cells from stem cells is the most recent and promising alternative. In particular, the optimization of in vitro strategies to differentiate human embryonic stem cells into mature insulin-secreting β cells has made considerable progress and recently led to the first clinical trial of stem cell treatment for T1D. Finally, the discovery that it is possible to derive human induced pluripotent stem cells from somatic cells has raised the possibility that a sufficient amount of patient-specific β cells can be derived from patients through cell reprogramming and differentiation, suggesting that in the future there might be a cell therapy without immunosuppression.


β Cell replacement Islet transplantation Xenotransplantation Pluripotent stem cells 


Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical standard

All works cited in this review have been published in journals that require approval by the Ethics Committees of the conducted experiments.

Human and animal rights

This article does not contain any studies with human or animal subjects performed by any of the authors.

Informed consent

All works cited in this review have been published in journals that require that informed consents of participants to reported clinical trials are collected.


  1. 1.
    Mannucci E, Monami M, Dicembrini I et al (2014) Achieving HbA1c targets in clinical trials and in the real world: a systematic review and meta-analysis. J Endocrinol Invest 37:477–495. doi: 10.1007/s40618-014-0069-6 CrossRefPubMedGoogle Scholar
  2. 2.
    Van Belle TL, Coppieters KT, von Herrath MG (2011) Type 1 diabetes: etiology, immunology, and therapeutic strategies. Physiol Rev 91:79–118. doi: 10.1152/physrev.00003.2010 CrossRefPubMedGoogle Scholar
  3. 3.
    Lind M, Svensson A-M, Kosiborod M et al (2014) Glycemic control and excess mortality in type 1 diabetes. N Engl J Med 371:1972–1982. doi: 10.1056/NEJMoa1408214 CrossRefPubMedGoogle Scholar
  4. 4.
    Saudek CD, Duckworth WC, Giobbie-Hurder A et al (1996) Implantable insulin pump vs multiple-dose insulin for non-insulin-dependent diabetes mellitus: a randomized clinical trial. Department of Veterans Affairs Implantable Insulin Pump Study Group. JAMA 276:1322–1327CrossRefPubMedGoogle Scholar
  5. 5.
    Maffi P, Secchi A (2015) Clinical results of islet transplantation. Pharmacol Res 98:86–91. doi: 10.1016/j.phrs.2015.04.010 CrossRefPubMedGoogle Scholar
  6. 6.
    Venturini M, Angeli E, Maffi P et al (2005) Technique, complications, and therapeutic efficacy of percutaneous transplantation of human pancreatic islet cells in type 1 diabetes: the role of US. Radiology 234:617–624. doi: 10.1148/radiol.2342031356 CrossRefPubMedGoogle Scholar
  7. 7.
    Warnock GL, Kneteman NM, Ryan EA et al (1989) Continued function of pancreatic islets after transplantation in type I diabetes. Lancet 334:570–572. doi: 10.1016/S0140-6736(89)90701-0 CrossRefGoogle Scholar
  8. 8.
    Scharp DW, Lacy PE, Santiago JV et al (1990) Insulin independence after islet transplantation into type I diabetic patient. Diabetes 39:515–518CrossRefPubMedGoogle Scholar
  9. 9.
    Piemonti L, Pileggi A (2013) 25 Years of the Ricordi automated method for islet isolation. Cellr4 1(1):e128. Accessed 29 Dec 2015
  10. 10.
    Bertuzzi F, Verzaro R, Provenzano V, Ricordi C (2007) Brittle type 1 diabetes mellitus. Curr Med Chem 14:1739–1744CrossRefPubMedGoogle Scholar
  11. 11.
    Ballinger WF, Lacy PE (1972) Transplantation of intact pancreatic islets in rats. Surgery 72:175–186PubMedGoogle Scholar
  12. 12.
    Kemp CB, Knight MJ, Scharp DW et al (1973) Effect of transplantation site on the results of pancreatic islet isografts in diabetic rats. Diabetologia 9:486–491CrossRefPubMedGoogle Scholar
  13. 13.
    Najarian JS, Sutherland DE, Matas AJ et al (1977) Human islet transplantation: a preliminary report. Transplant Proc 9:233–236PubMedGoogle Scholar
  14. 14.
    Ricordi C, Lacy PE, Finke EH et al (1988) Automated method for isolation of human pancreatic islets. Diabetes 37:413–420CrossRefPubMedGoogle Scholar
  15. 15.
    Oberholzer J, Triponez F, Mage R et al (2000) Human islet transplantation: lessons from 13 autologous and 13 allogeneic transplantations. Transplantation 69:1115–1123CrossRefPubMedGoogle Scholar
  16. 16.
    Secchi A, Socci C, Maffi P et al (1997) Islet transplantation in IDDM patients. Diabetologia 40:225–231CrossRefPubMedGoogle Scholar
  17. 17.
    Shapiro AM, Lakey JR, Ryan EA et al (2000) Islet transplantation in seven patients with type 1 diabetes mellitus using a glucocorticoid-free immunosuppressive regimen. N Engl J Med 343:230–238. doi: 10.1056/NEJM200007273430401 CrossRefPubMedGoogle Scholar
  18. 18.
    Shapiro AMJ, Ricordi C, Hering BJ et al (2006) International trial of the Edmonton protocol for islet transplantation. N Engl J Med 355:1318–1330. doi: 10.1056/NEJMoa061267 CrossRefPubMedGoogle Scholar
  19. 19.
    Brennan DC, Kopetskie HA, Sayre PH et al (2015) Long-term follow-up of the edmonton protocol of islet transplantation in the United States. Am J Transplant. doi: 10.1111/ajt.13458 PubMedGoogle Scholar
  20. 20.
    Barton FB, Rickels MR, Alejandro R et al (2012) Improvement in outcomes of clinical islet transplantation: 1999–2010. Diabetes Care 35:1436–1445. doi: 10.2337/dc12-0063 CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Brooks AM, Walker N, Aldibbiat A et al (2013) Attainment of metabolic goals in the integrated UK islet transplant program with locally isolated and transported preparations. Am J Transplant 13:3236–3243. doi: 10.1111/ajt.12469 CrossRefPubMedGoogle Scholar
  22. 22.
    Vantyghem MC, Kerr-Conte J, Arnalsteen L et al (2009) Primary graft function, metabolic control, and graft survival after islet transplantation. Diabetes Care 32:1473–1478. doi: 10.2337/dc08-1685 CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Lablanche S, Borot S, Wojtusciszyn A et al (2015) Five-year metabolic, functional, and safety results of patients with type 1 diabetes transplanted with allogenic islets within the Swiss-French GRAGIL network. Diabetes Care 38:1714–1722. doi: 10.2337/dc15-0094 CrossRefPubMedGoogle Scholar
  24. 24.
    Qi M, Kinzer K, Danielson KK et al (2014) Five-year follow-up of patients with type 1 diabetes transplanted with allogeneic islets: the UIC experience. Acta Diabetol 51:833–843. doi: 10.1007/s00592-014-0627-6 CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Bellin MD, Barton FB, Heitman A et al (2012) Potent induction immunotherapy promotes long-term insulin independence after islet transplantation in type 1 diabetes. Am J Transplant 12:1576–1583. doi: 10.1111/j.1600-6143.2011.03977.x CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Shapiro AMJ (2011) State of the art of clinical islet transplantation and novel protocols of immunosuppression. Curr Diabetes Rep 11:345–354. doi: 10.1007/s11892-011-0217-8 CrossRefGoogle Scholar
  27. 27.
    Posselt AM, Szot GL, Frassetto LA et al (2010) Islet transplantation in type 1 diabetic patients using calcineurin inhibitor-free immunosuppressive protocols based on T-cell adhesion or costimulation blockade. Transplantation 90(12):1595–1601CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Nijhoff MF, Engelse MA, Dubbeld J et al (2015) Glycemic stability through islet-after-kidney transplantation using an alemtuzumab-based induction regimen and long-term triple-maintenance immunosuppression. Am J Transplant. doi: 10.1111/ajt.13425 PubMedGoogle Scholar
  29. 29.
    Maffi P, Berney T, Nano R et al (2014) Calcineurin inhibitor-free immunosuppressive regimen in type 1 diabetes patients receiving islet transplantation: single-group phase 1/2 trial. Transplantation. doi: 10.1097/TP.0000000000000396 PubMedGoogle Scholar
  30. 30.
    Posselt AM, Bellin MD, Tavakol M et al (2010) Islet transplantation in type 1 diabetics using an immunosuppressive protocol based on the anti-LFA-1 antibody efalizumab. Am J Transplant 10:1870–1880. doi: 10.1111/j.1600-6143.2010.03073.x CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    El Khatib MM, Sakuma T, Tonne JM et al (2015) β-Cell-targeted blockage of PD1 and CTLA4 pathways prevents development of autoimmune diabetes and acute allogeneic islets rejection. Gene Ther 22:430–438. doi: 10.1038/gt.2015.18 CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Watanabe M, Yamashita K, Suzuki T et al (2013) ASKP1240, a fully human anti-CD40 monoclonal antibody, prolongs pancreatic islet allograft survival in nonhuman primates. Am J Transplant 13:1976–1988. doi: 10.1111/ajt.12330 CrossRefPubMedGoogle Scholar
  33. 33.
    Citro A, Cantarelli E, Maffi P et al (2012) CXCR1/2 inhibition enhances pancreatic islet survival after transplantation. J Clin Invest 122:3647–3651. doi: 10.1172/JCI63089 CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Kandaswamy R, Skeans MA, Gustafson SK et al (2015) OPTN/SRTR 2013 annual data report: pancreas. Am J Transplant 15:1–20. doi: 10.1111/ajt.13196 CrossRefPubMedGoogle Scholar
  35. 35.
    Klymiuk N, Aigner B, Brem G, Wolf E (2010) Genetic modification of pigs as organ donors for xenotransplantation. Mol Reprod Dev 77:209–221PubMedGoogle Scholar
  36. 36.
    Groth CG, Korsgren O, Tibell A et al (1994) Transplantation of porcine fetal pancreas to diabetic patients. Lancet (London, England) 344:1402–1404CrossRefGoogle Scholar
  37. 37.
    Galili U, Shohet SB, Kobrin E et al (1988) Man, apes, and Old World monkeys differ from other mammals in the expression of alpha-galactosyl epitopes on nucleated cells. J Biol Chem 263:17755–17762PubMedGoogle Scholar
  38. 38.
    Patience C, Takeuchi Y, Weiss RA (1997) Infection of human cells by an endogenous retrovirus of pigs. Nat Med 3:282–286CrossRefPubMedGoogle Scholar
  39. 39.
    Cardona K, Korbutt GS, Milas Z et al (2006) Long-term survival of neonatal porcine islets in nonhuman primates by targeting costimulation pathways. Nat Med 12:304–306. doi: 10.1038/nm1375 CrossRefPubMedGoogle Scholar
  40. 40.
    Hering BJ, Wijkstrom M, Graham ML et al (2006) Prolonged diabetes reversal after intraportal xenotransplantation of wild-type porcine islets in immunosuppressed nonhuman primates. Nat Med 12:301–303. doi: 10.1038/nm1369 CrossRefPubMedGoogle Scholar
  41. 41.
    Shin JS, Kim JM, Kim JS et al (2015) Long-term control of diabetes in immunosuppressed nonhuman primates (NHP) by the transplantation of adult porcine islets. Am J Transplant 15:2837–2850. doi: 10.1111/ajt.13345 CrossRefPubMedGoogle Scholar
  42. 42.
    Thompson P, Badell IR, Lowe M et al (2011) Islet xenotransplantation using gal-deficient neonatal donors improves engraftment and function. Am J Transplant 11:2593–2602. doi: 10.1111/j.1600-6143.2011.03720.x CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Bottino R, Wijkstrom M, van der Windt DJ et al (2014) Pig-to-monkey islet xenotransplantation using multi-transgenic pigs. Am J Transplant 14:2275–2287. doi: 10.1111/ajt.12868 CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Rayat GR, Rajotte RV, Ao Z, Korbutt GS (2000) Microencapsulation of neonatal porcine islets: protection from human antibody/complement-mediated cytolysis in vitro and long-term reversal of diabetes in nude mice. Transplantation 69:1084–1090CrossRefPubMedGoogle Scholar
  45. 45.
    Dufrane D, Goebbels R-M, Gianello P (2010) Alginate macroencapsulation of pig islets allows correction of streptozotocin-induced diabetes in primates up to 6 months without immunosuppression. Transplantation 90:1054–1062. doi: 10.1097/TP.0b013e3181f6e267 CrossRefPubMedGoogle Scholar
  46. 46.
    Elliott RB, Escobar L, Tan PLJ et al (2007) Live encapsulated porcine islets from a type 1 diabetic patient 9.5 yr after xenotransplantation. Xenotransplantation 14:157–161. doi: 10.1111/j.1399-3089.2007.00384.x CrossRefPubMedGoogle Scholar
  47. 47.
    Valdés-González RA, Dorantes LM, Garibay GN et al (2005) Xenotransplantation of porcine neonatal islets of Langerhans and Sertoli cells: a 4-year study. Eur J Endocrinol 153:419–427. doi: 10.1530/eje.1.01982 CrossRefPubMedGoogle Scholar
  48. 48.
    Wang W, Mo Z, Ye B et al (2011) A clinical trial of xenotransplantation of neonatal pig islets for diabetic patients. Zhong Nan Da Xue Xue Bao Yi Xue Ban 36:1134–1140. doi: 10.3969/j.issn.1672-7347.2011.12.002 PubMedGoogle Scholar
  49. 49.
    Teta M, Long SY, Wartschow LM et al (2005) Very slow turnover of beta-cells in aged adult mice. Diabetes 54:2557–2567CrossRefPubMedGoogle Scholar
  50. 50.
    Wang P, Fiaschi-Taesch NM, Vasavada RC et al (2015) Diabetes mellitus–advances and challenges in human β-cell proliferation. Nat Rev Endocrinol 11:201–212. doi: 10.1038/nrendo.2015.9 CrossRefPubMedGoogle Scholar
  51. 51.
    Levine F, Wang S, Beattie GM et al (1995) Development of a cell line from the human fetal pancreas. Transplant Proc 27:3410PubMedGoogle Scholar
  52. 52.
    De la Tour D, Halvorsen T, Demeterco C et al (2001) Beta-cell differentiation from a human pancreatic cell line in vitro and in vivo. Mol Endocrinol 15:476–483PubMedGoogle Scholar
  53. 53.
    Narushima M, Kobayashi N, Okitsu T et al (2005) A human beta-cell line for transplantation therapy to control type 1 diabetes. Nat Biotechnol 23:1274–1282CrossRefPubMedGoogle Scholar
  54. 54.
    Ravassard P, Hazhouz Y, Pechberty S et al (2011) A genetically engineered human pancreatic β cell line exhibiting glucose-inducible insulin secretion. J Clin Invest 121:3589–3597CrossRefPubMedPubMedCentralGoogle Scholar
  55. 55.
    Scharfmann R, Pechberty S, Hazhouz Y et al (2014) Development of a conditionally immortalized human pancreatic β cell line. J Clin Invest 124:2087–2098. doi: 10.1172/JCI72674 CrossRefPubMedPubMedCentralGoogle Scholar
  56. 56.
    Jones PM, Courtney ML, Burns CJ, Persaud SJ (2008) Cell-based treatments for diabetes. Drug Discov Today 13:888–893. doi: 10.1016/j.drudis.2008.06.014 CrossRefPubMedGoogle Scholar
  57. 57.
    Thomson JA, Itskovitz-Eldor J, Shapiro SS et al (1998) Embryonic stem cell lines derived from human blastocysts. Science 282:1145–1147CrossRefPubMedGoogle Scholar
  58. 58.
    D’Amour KA, Bang AG, Eliazer S et al (2006) Production of pancreatic hormone-expressing endocrine cells from human embryonic stem cells. Nat Biotechnol 24:1392–1401. doi: 10.1038/nbt1259 CrossRefPubMedGoogle Scholar
  59. 59.
    Jiang W, Shi Y, Zhao D et al (2007) In vitro derivation of functional insulin-producing cells from human embryonic stem cells. Cell Res 17:333–344. doi: 10.1038/cr.2007.28 CrossRefPubMedGoogle Scholar
  60. 60.
    Jiang J, Au M, Lu K et al (2007) Generation of insulin-producing islet-like clusters from human embryonic stem cells. Stem Cells 25:1940–1953. doi: 10.1634/stemcells.2006-0761 CrossRefPubMedGoogle Scholar
  61. 61.
    Kroon E, Martinson LA, Kadoya K et al (2008) Pancreatic endoderm derived from human embryonic stem cells generates glucose-responsive insulin-secreting cells in vivo. Nat Biotechnol 26:443–452CrossRefPubMedGoogle Scholar
  62. 62.
    Schulz TC, Young HY, Agulnick AD et al (2012) A scalable system for production of functional pancreatic progenitors from human embryonic stem cells. PLoS ONE 7:e37004CrossRefPubMedPubMedCentralGoogle Scholar
  63. 63.
    Chen S, Borowiak M, Fox JL et al (2009) A small molecule that directs differentiation of human ESCs into the pancreatic lineage. Nat Chem Biol 5:258–265. doi: 10.1038/nchembio.154 CrossRefPubMedGoogle Scholar
  64. 64.
    Rezania A, Bruin JE, Xu J et al (2013) Enrichment of human embryonic stem cell-derived NKX6.1-expressing pancreatic progenitor cells accelerates the maturation of insulin-secreting cells in vivo. Stem Cells 31:2432–2442. doi: 10.1002/stem.1489 CrossRefPubMedGoogle Scholar
  65. 65.
    Nostro MC, Sarangi F, Yang C et al (2015) Efficient generation of NKX6-1+ pancreatic progenitors from multiple human pluripotent stem cell lines. Stem Cell Rep 4:591–604. doi: 10.1016/j.stemcr.2015.02.017 CrossRefGoogle Scholar
  66. 66.
    Pagliuca FW, Millman JR, Gürtler M et al (2014) Generation of functional human pancreatic β cells in vitro. Cell 159:428–439. doi: 10.1016/j.cell.2014.09.040 CrossRefPubMedPubMedCentralGoogle Scholar
  67. 67.
    Rezania A, Bruin JE, Arora P et al (2014) Reversal of diabetes with insulin-producing cells derived in vitro from human pluripotent stem cells. Nat Biotechnol. doi: 10.1038/nbt.3033 PubMedGoogle Scholar
  68. 68.
    Kelly OG, Chan MY, Martinson LA et al (2011) Cell-surface markers for the isolation of pancreatic cell types derived from human embryonic stem cells. Nat Biotechnol 29:750–756CrossRefPubMedGoogle Scholar
  69. 69.
    Jiang W, Sui X, Zhang D et al (2011) CD24: a novel surface marker for PDX1-positive pancreatic progenitors derived from human embryonic stem cells. Stem Cells 29:609–617CrossRefPubMedGoogle Scholar
  70. 70.
    Osafune K, Caron L, Borowiak M et al (2008) Marked differences in differentiation propensity among human embryonic stem cell lines. Nat Biotechnol 26:313–315CrossRefPubMedGoogle Scholar
  71. 71.
    Takahashi K, Yamanaka S (2006) Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126:663–676. doi: 10.1016/j.cell.2006.07.024 CrossRefPubMedGoogle Scholar
  72. 72.
    Yu J, Vodyanik MA, Smuga-Otto K et al (2007) Induced pluripotent stem cell lines derived from human somatic cells. Science 318:1917–1920. doi: 10.1126/science.1151526 CrossRefPubMedGoogle Scholar
  73. 73.
    Takahashi K, Tanabe K, Ohnuki M et al (2007) Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131:861–872. doi: 10.1016/j.cell.2007.11.019 CrossRefPubMedGoogle Scholar
  74. 74.
    Tateishi K, He J, Taranova O et al (2008) Generation of insulin-secreting islet-like clusters from human skin fibroblasts. J Biol Chem 283:31601–31607. doi: 10.1074/jbc.M806597200 CrossRefPubMedGoogle Scholar
  75. 75.
    Schroeder IS, Rolletschek A, Blyszczuk P et al (2006) Differentiation of mouse embryonic stem cells to insulin-producing cells. Nat Protoc 1:495–507. doi: 10.1038/nprot.2006.71 CrossRefPubMedGoogle Scholar
  76. 76.
    Alipio Z, Liao W, Roemer EJ et al (2010) Reversal of hyperglycemia in diabetic mouse models using induced-pluripotent stem (iPS)-derived pancreatic beta-like cells. Proc Natl Acad Sci USA 107:13426–13431. doi: 10.1073/pnas.1007884107 CrossRefPubMedPubMedCentralGoogle Scholar
  77. 77.
    Thatava T, Nelson TJ, Edukulla R et al (2011) Indolactam V/GLP-1-mediated differentiation of human iPS cells into glucose-responsive insulin-secreting progeny. Gene Ther 18:283–293. doi: 10.1038/gt.2010.145 CrossRefPubMedGoogle Scholar
  78. 78.
    Zhang D, Jiang W, Liu M et al (2009) Highly efficient differentiation of human ES cells and iPS cells into mature pancreatic insulin-producing cells. Cell Res 19:429–438. doi: 10.1038/cr.2009.28 CrossRefPubMedGoogle Scholar
  79. 79.
    Kunisada Y, Tsubooka-Yamazoe N, Shoji M, Hosoya M (2012) Small molecules induce efficient differentiation into insulin-producing cells from human induced pluripotent stem cells. Stem Cell Res 8:274–284. doi: 10.1016/j.scr.2011.10.002 CrossRefPubMedGoogle Scholar
  80. 80.
    Hua H, Shang L, Martinez H et al (2013) iPSC-derived β cells model diabetes due to glucokinase deficiency. J Clin Invest 123:3146–3153. doi: 10.1172/JCI67638 CrossRefPubMedPubMedCentralGoogle Scholar
  81. 81.
    Nostro MC, Sarangi F, Ogawa S et al (2011) Stage-specific signaling through TGFβ family members and WNT regulates patterning and pancreatic specification of human pluripotent stem cells. Development 138:861–871. doi: 10.1242/dev.055236 CrossRefPubMedPubMedCentralGoogle Scholar
  82. 82.
    Pellegrini S, Ungaro F, Mercalli A et al (2015) Human induced pluripotent stem cells differentiate into insulin-producing cells able to engraft in vivo. Acta Diabetol 52:1025–1035. doi: 10.1007/s00592-015-0726-z CrossRefPubMedGoogle Scholar
  83. 83.
    Maehr R, Chen S, Snitow M et al (2009) Generation of pluripotent stem cells from patients with type 1 diabetes. Proc Natl Acad Sci USA 106:15768–15773. doi: 10.1073/pnas.0906894106 CrossRefPubMedPubMedCentralGoogle Scholar
  84. 84.
    Nakagawa M, Koyanagi M, Tanabe K et al (2008) Generation of induced pluripotent stem cells without Myc from mouse and human fibroblasts. Nat Biotechnol 26:101–106. doi: 10.1038/nbt1374 CrossRefPubMedGoogle Scholar
  85. 85.
    Singh VK, Kalsan M, Kumar N et al (2015) Induced pluripotent stem cells: applications in regenerative medicine, disease modeling, and drug discovery. Front Cell Dev Biol. doi: 10.3389/fcell.2015.00002 PubMedPubMedCentralGoogle Scholar
  86. 86.
    Motté E, Szepessy E, Suenens K et al (2014) Composition and function of macroencapsulated human embryonic stem cell-derived implants: comparison with clinical human islet cell grafts. Am J Physiol Endocrinol Metab 307:E838–E846. doi: 10.1152/ajpendo.00219.2014 CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Italia 2016

Authors and Affiliations

  1. 1.Diabetes Research Institute, IRCCS San Raffaele Scientific InstituteMilanItaly

Personalised recommendations