Skip to main content
Log in

Transplantable bioartificial pancreas devices: current status and future prospects

Langenbeck's Archives of Surgery Aims and scope Submit manuscript

Abstract

Background

Islet transplantation has become a valuable therapy for patients with diabetes mellitus type 1.However, only selected patients with exhausted insulin therapy characterized by instable metabolic control and repeated severe hypoglycemia are transplant candidates. This strict indication is mainly due to the requirement for lifelong immunosuppression and the critical shortage for donor organs. Therefore, numerous research activities address these issues in order to provide beta cell replacement therapy to a broader cohort of patients with diabetes.

Methods

The encapsulation of pancreatic islets within mainly alginate-based macro- or microcapsules withvarious physical configurations may allow protecting the islet graft without the need for immunosuppressive agents and moreover expanding the donor pool to animal tissue and novel insulin-producing cells. Despite major advances in encapsulation technology, a significant translation into clinical application is not evident. There are still issues that need to be resolved associated with graft oxygenation, immunprotection, inflammatory response, material biocompatibility, and transplantation site to list some of them.

Conclusion

The recent advances in xenotransplantation and particularly in the field of stem cell-derived beta cells have generated a renewed scientific interest in encapsulation. This review aims to provide an overview on current encapsulation technologies as a treatment modality in cell replacement therapy for type 1 diabetes.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Gruessner RW, Gruessner AC (2014) What defines success in pancreas and islet transplantation-insulin independence or prevention of hypoglycemia? A review. Transplant Proc 46(6):1898–1899

    Article  CAS  PubMed  Google Scholar 

  2. Maffi P, Secchi A (2015).Clinical results of islet transplantation. Pharmacol Res

  3. 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 (2014) 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

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  4. Robertson RP (2015) Islet transplantation for type 1 diabetes, 2015: what have we learned from alloislet and autoislet successes? Diabetes Care 38(6):1030–1035

    Article  PubMed  Google Scholar 

  5. Matsumoto S, Takita M, Chaussabel D, Noguchi H, Shimoda M, Sugimoto K, Itoh T, Chujo D, SoRelle J, Onaca N, Naziruddin B, Levy MF (2011) Improving efficacy of clinical islet transplantation with iodixanol-based islet purification, thymoglobulin induction, and blockage of IL-1β and TNF-α. Cell Transplant 20(10):1641–1647

    Article  PubMed  Google Scholar 

  6. Fridell JA, Rogers J, Stratta RJ (2010) The pancreas allograft donor: current status, controversies, and challenges for the future. Clin Transpl 24(4):433–449

    Article  Google Scholar 

  7. Stegall MD, Dean PG, Sung R, Guidinger MK, McBride MA, Sommers C, Basadonna G, Stock PG, Leichtman AB (2007) The rationale for the new deceased donor pancreas allocation schema. Transplantation 83(9):1156–1161

    Article  PubMed  Google Scholar 

  8. Nilsson B, Ekdahl KN, Korsgren O (2011) Control of instant blood-mediated inflammatory reaction to improve islets of Langerhans engraftment. Curr Opin Organ Transplant 16(6):620–626

    Article  CAS  PubMed  Google Scholar 

  9. Krishnan R, Alexander M, Robles L, Foster CE 3rd, Lakey JR (2014) Islet and stem cell encapsulation for clinical transplantation. Rev Diabet Stud 11(1):84–101

    Article  PubMed Central  PubMed  Google Scholar 

  10. Scharp DW, Mason NS, Sparks RE (1984) Islet immuno-isolation: the use of hybrid artificial organs to prevent islet tissue rejection. World J Surg 8(2):221–229

    Article  CAS  PubMed  Google Scholar 

  11. Algire GH, Weaver JM, Prehn RT (1954) Growth of cells in vivo in diffusion chambers. I. Survival of homografts in immunized mice. J Natl Cancer Inst 15(3):493–507

    CAS  PubMed  Google Scholar 

  12. Weaver JM, Algire GH, Prehn RT (1955) The growth of cells in vivo in diffusion chambers. II. The role of cells in the destruction of homografts in mice. J Natl Cancer Inst 15(6):1737–1767

    CAS  PubMed  Google Scholar 

  13. Algire GH, Weaver JM, Prehn RT (1957) Studies on tissue homotransplantation in mice, using diffusion-chamber methods. Ann N Y Acad Sci 64(5):1009–1013

    Article  CAS  PubMed  Google Scholar 

  14. Algire GH, Borders ML, Evans VJ (1958) Studies of heterografts in diffusion chambers in mice. J Natl Cancer Inst 20(6):1187–1201

    CAS  PubMed  Google Scholar 

  15. Algire GH (1957) Summary of studies of transplantation of homologous tissues. Fed Proc 16(2):601–602

    CAS  PubMed  Google Scholar 

  16. Algire GH (1957) Diffusion-chamber techniques for studies of cellular immunity. Ann N Y Acad Sci 69(4):663–667

    Article  CAS  PubMed  Google Scholar 

  17. Monaco AP, Maki T, Ozato H, Carretta M, Sullivan SJ, Borland KM, Mahoney MD, Chick WL, Muller TE, Wolfrum J et al (1991) Transplantation of islet allografts and xenografts in totally pancreatectomized diabetic dogs using the hybrid artificial pancreas. Ann Surg 214(3):339–360, discussion 361-332

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  18. Hymer WC, Wilbur DL, Page R, Hibbard E, Kelsey RC, Hatfield JM (1981) Pituitary hollow fiber units in vivo and in vitro. Neuroendocrinology 32(6):339–349

    Article  CAS  PubMed  Google Scholar 

  19. Zekorn T, Siebers U, Filip L, Mauer K, Schmitt U, Bretzel RG, Federlin K (1989) Bioartificial pancreas: the use of different hollow fibers as a diffusion chamber. Transplant Proc 21(1 Pt 3):2748–2750

    CAS  PubMed  Google Scholar 

  20. Maki T, Ubhi CS, Sanchez-Farpon H, Sullivan SJ, Borland K, Muller TE, Solomon BA, Chick WL, Monaco AP (1991) Successful treatment of diabetes with the biohybrid artificial pancreas in dogs. Transplantation 51(1):43–51

    Article  CAS  PubMed  Google Scholar 

  21. Maki T, Mullon CJ, Solomon BA, Monaco AP (1995) Novel delivery of pancreatic islet cells to treat insulin-dependent diabetes mellitus. Clin Pharmacokinet 28(6):471–482

    Article  CAS  PubMed  Google Scholar 

  22. Rafael E, Wernerson A, Arner P, Wu GS, Tibell A (1999) In vivo evaluation of glucose permeability of an immunoisolation device intended for islet transplantation: a novel application of the microdialysis technique. Cell Transplant 8(3):317–326

    CAS  PubMed  Google Scholar 

  23. Rafael E, Wernerson A, Arner P, Tibell A (1999) In vivo studies on insulin permeability of an immunoisolation device intended for islet transplantation using the microdialysis technique. Eur Surg Res 31(3):249–258

    Article  CAS  PubMed  Google Scholar 

  24. Scharp DW, Marchetti P (2014) Encapsulated islets for diabetes therapy: history, current progress, and critical issues requiring solution. Adv Drug Deliv Rev 67–68:35–73

    Article  PubMed  Google Scholar 

  25. de Groot M, Schuurs TA, van Schilfgaarde R (2004) Causes of limited survival of microencapsulated pancreatic islet grafts. J Surg Res 121(1):141–150

    Article  PubMed  Google Scholar 

  26. Barkai U, Weir GC, Colton CK, Ludwig B, Bornstein SR, Brendel MD, Neufeld T, Bremer C, Leon A, Evron Y, Yavriyants K, Azarov D, Zimermann B, Maimon S, Shabtay N, Balyura M, Rozenshtein T, Vardi P, Bloch K, de Vos P, Rotem A (2013) Enhanced oxygen supply improves islet viability in a new bioartificial pancreas. Cell Transplant 22(8):1463–1476

    Article  PubMed  Google Scholar 

  27. Ludwig B, Zimerman B, Steffen A, Yavriants K, Azarov D, Reichel A, Vardi P, German T, Shabtay N, Rotem A, Evron Y, Neufeld T, Mimon S, Ludwig S, Brendel MD, Bornstein SR, Barkai U (2010) A novel device for islet transplantation providing immune protection and oxygen supply. Horm Metab Res 42(13):918–922

    Article  CAS  PubMed  Google Scholar 

  28. Neufeld T, Ludwig B, Barkai U, Weir GC, Colton CK, Evron Y, Balyura M, Yavriyants K, Zimermann B, Azarov D, Maimon S, Shabtay N, Rozenshtein T, Lorber D, Steffen A, Willenz U, Bloch K, Vardi P, Taube R, de Vos P, Lewis EC, Bornstein SR, Rotem A (2013) The efficacy of an immunoisolating membrane system for islet xenotransplantation in minipigs. PLoS One 8(8):e70150

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  29. Ludwig B, Rotem A, Schmid J, Weir GC, Colton CK, Brendel MD, Neufeld T, Block NL, Yavriyants K, Steffen A, Ludwig S, Chavakis T, Reichel A, Azarov D, Zimermann B, Maimon S, Balyura M, Rozenshtein T, Shabtay N, Vardi P, Bloch K, de Vos P, Schally AV, Bornstein SR, Barkai U (2012) Improvement of islet function in a bioartificial pancreas by enhanced oxygen supply and growth hormone releasing hormone agonist. Proc Natl Acad Sci U S A 109(13):5022–5027

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  30. Ludwig B, Reichel A, Steffen A, Zimerman B, Schally AV, Block NL, Colton CK, Ludwig S, Kersting S, Bonifacio E, Solimena M, Gendler Z, Rotem A, Barkai U, Bornstein SR (2013) Transplantation of human islets without immunosuppression. Proc Natl Acad Sci U S A 110(47):19054–19058

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  31. Lanza RP, Beyer AM, Staruk JE, Chick WL (1993) Biohybrid artificial pancreas. Long-term function of discordant islet xenografts in streptozotocin diabetic rats. Transplantation 56(5):1067–1072

    Article  CAS  PubMed  Google Scholar 

  32. Lanza RP, Borland KM, Lodge P, Carretta M, Sullivan SJ, Muller TE, Solomon BA, Maki T, Monaco AP, Chick WL (1992) Treatment of severely diabetic pancreatectomized dogs using a diffusion-based hybrid pancreas. Diabetes 41(7):886–889

    Article  CAS  PubMed  Google Scholar 

  33. Lanza RP, Borland KM, Staruk JE, Appel MC, Solomon BA, Chick WL (1992) Transplantation of encapsulated canine islets into spontaneously diabetic BB/Wor rats without immunosuppression. Endocrinology 131(2):637–642

    CAS  PubMed  Google Scholar 

  34. Merani S, Toso C, Emamaullee J, Shapiro AM (2008) Optimal implantation site for pancreatic islet transplantation. Br J Surg 95(12):1449–1461

    Article  CAS  PubMed  Google Scholar 

  35. de Vos P, Spasojevic M, Faas MM (2010) Treatment of diabetes with encapsulated islets. Adv Exp Med Biol 670:38–53

    Article  PubMed  Google Scholar 

  36. Teramura Y, Iwata H (2010) Bioartificial pancreas microencapsulation and conformal coating of islet of Langerhans. Adv Drug Deliv Rev 62(7–8):827–840

    Article  CAS  PubMed  Google Scholar 

  37. Soon-Shiong P, Feldman E, Nelson R, Komtebedde J, Smidsrod O, Skjak-Braek G, Espevik T, Heintz R, Lee M (1992) Successful reversal of spontaneous diabetes in dogs by intraperitoneal microencapsulated islets. Transplantation 54(5):769–774

    Article  CAS  PubMed  Google Scholar 

  38. Lanza RP, Ecker DM, Kuhtreiber WM, Marsh JP, Ringeling J, Chick WL (1999) Transplantation of islets using microencapsulation: studies in diabetic rodents and dogs. J Mol Med (Berl) 77(1):206–210

    Article  CAS  Google Scholar 

  39. Dufrane D, Gianello P (2012) Macro- or microencapsulation of pig islets to cure type 1 diabetes. World J Gastroenterol 18(47):6885–6893

    Article  PubMed Central  PubMed  Google Scholar 

  40. Calafiore R (1992) Transplantation of microencapsulated pancreatic human islets for therapy of diabetes mellitus. A preliminary report. Asaio J 38(1):34–37

    Article  CAS  PubMed  Google Scholar 

  41. Paredes Juarez GA, Spasojevic M, Faas MM, de Vos P (2014) Immunological and technical considerations in application of alginate-based microencapsulation systems. Front Bioeng Biotechnol 2:26

    Article  PubMed Central  PubMed  Google Scholar 

  42. Opara EC, McQuilling JP, Farney AC (2013) Microencapsulation of pancreatic islets for use in a bioartificial pancreas. Methods Mol Biol 1001:261–266

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  43. Calafiore R, Basta G (2014) Clinical application of microencapsulated islets: actual prospectives on progress and challenges. Adv Drug Deliv Rev 67–68:84–92

    Article  PubMed  Google Scholar 

  44. De Vos P, Van Straaten JF, Nieuwenhuizen AG, de Groot M, Ploeg RJ, De Haan BJ, Van Schilfgaarde R (1999) Why do microencapsulated islet grafts fail in the absence of fibrotic overgrowth? Diabetes 48(7):1381–1388

    Article  PubMed  Google Scholar 

  45. Matsumoto S, Tan P, Baker J, Durbin K, Tomiya M, Azuma K, Doi M, Elliott RB (2014) Clinical porcine islet xenotransplantation under comprehensive regulation. Transplant Proc 46(6):1992–1995

    Article  CAS  PubMed  Google Scholar 

  46. Matsuda T, Kitamura T, Iwata H, Takano H, Akutsu T (1988) A hybrid artificial vascular graft based upon an organ reconstruction model. Significance and design criteria of an artificial basement membrane. ASAIO Trans 34(3):640–643

    CAS  PubMed  Google Scholar 

  47. Wang T, Lacik I, Brissova M, Anilkumar AV, Prokop A, Hunkeler D, Green R, Shahrokhi K, Powers AC (1997) An encapsulation system for the immunoisolation of pancreatic islets. Nat Biotechnol 15(4):358–362

    Article  CAS  PubMed  Google Scholar 

  48. Wang T, Adcock J, Kuhtreiber W, Qiang D, Salleng KJ, Trenary I, Williams P (2008) Successful allotransplantation of encapsulated islets in pancreatectomized canines for diabetic management without the use of immunosuppression. Transplantation 85(3):331–337

    Article  PubMed  Google Scholar 

  49. Drumheller PD, Elbert DL, Hubbell JA (1994) Multifunctional poly(ethylene glycol) semi-interpenetrating polymer networks as highly selective adhesive substrates for bioadhesive peptide grafting. Biotechnol Bioeng 43(8):772–780

    Article  CAS  PubMed  Google Scholar 

  50. Sawhney AS, Pathak CP, Hubbell JA (1993) Interfacial photopolymerization of poly(ethylene glycol)-based hydrogels upon alginate-poly(l-lysine) microcapsules for enhanced biocompatibility. Biomaterials 14(13):1008–1016

    Article  CAS  PubMed  Google Scholar 

  51. Sawhney AS, Pathak CP, Hubbell JA (1994) Modification of islet of langerhans surfaces with immunoprotective poly(ethylene glycol) coatings via interfacial photopolymerization. Biotechnol Bioeng 44(3):383–386

    Article  CAS  PubMed  Google Scholar 

  52. Hill RS, Cruise GM, Hager SR, Lamberti FV, Yu X, Garufis CL, Yu Y, Mundwiler KE, Cole JF, Hubbell JA, Hegre OD, Scharp DW (1997) Immunoisolation of adult porcine islets for the treatment of diabetes mellitus. The use of photopolymerizable polyethylene glycol in the conformal coating of mass-isolated porcine islets. Ann N Y Acad Sci 831:332–343

    Article  CAS  PubMed  Google Scholar 

  53. Cruise GM, Hegre OD, Lamberti FV, Hager SR, Hill R, Scharp DS, Hubbell JA (1999) In vitro and in vivo performance of porcine islets encapsulated in interfacially photopolymerized poly(ethylene glycol) diacrylate membranes. Cell Transplant 8(3):293–306

  54. Tomei AA, Manzoli V, Fraker CA, Giraldo J, Velluto D, Najjar M, Pileggi A (2014) Device design and materials optimization of conformal coating for islets of Langerhans. Proc Natl Acad Sci U S A 111(29):10514–10519

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  55. Wilson JT, Cui W, Chaikof EL (2008) Layer-by-layer assembly of a conformal nanothin PEG coating for intraportal islet transplantation. Nano Lett 8(7):1940–1948

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  56. Gattas-Asfura KM, Stabler CL (2013) Bioorthogonal layer-by-layer encapsulation of pancreatic islets via hyperbranched polymers. ACS Appl Mater Interfaces 5(20):9964–9974

    Article  CAS  PubMed  Google Scholar 

  57. Teramura Y, Kaneda Y, Iwata H (2007) Islet-encapsulation in ultra-thin layer-by-layer membranes of poly(vinyl alcohol) anchored to poly(ethylene glycol)-lipids in the cell membrane. Biomaterials 28(32):4818–4825

    Article  CAS  PubMed  Google Scholar 

  58. Rengifo HR, Giraldo JA, Labrada I, Stabler CL (2014) Long-term survival of allograft murine islets coated via covalently stabilized polymers. Adv Healthcare Mater 3(7):1061–1070

    Article  CAS  Google Scholar 

  59. Zhi ZL, Kerby A, King AJ, Jones PM, Pickup JC (2012) Nano-scale encapsulation enhances allograft survival and function of islets transplanted in a mouse model of diabetes. Diabetologia 55(4):1081–1090

    Article  CAS  PubMed  Google Scholar 

  60. Ludwig B, Ludwig S, Steffen A, Saeger HD, Bornstein SR (2010) Islet versus pancreas transplantation in type 1 diabetes: competitive or complementary? Curr Diab Rep 10(6):506–511

    Article  PubMed  Google Scholar 

  61. van der Windt DJ, Echeverri GJ, Ijzermans JN, Cooper DK (2008) The choice of anatomical site for islet transplantation. Cell Transplant 17(9):1005–1014

    Article  PubMed  Google Scholar 

  62. van der Windt DJ, Bottino R, Casu A, Campanile N, Cooper DK (2007) Rapid loss of intraportally transplanted islets: an overview of pathophysiology and preventive strategies. Xenotransplantation 14(4):288–297

    Article  PubMed  Google Scholar 

  63. Robson SC, Cooper DK, d’Apice AJ (2000) Disordered regulation of coagulation and platelet activation in xenotransplantation. Xenotransplantation 7(3):166–176

    Article  CAS  PubMed  Google Scholar 

  64. Kim JH, Oh BJ, Lee HN, Park HS, Park SG, Park KS (2011) Endothelial colony-forming cell coating of pig islets prevents xenogeneic instant blood-mediated inflammatory reaction. Cell Transplant 20(11-12):1805–1815

    Article  PubMed  Google Scholar 

  65. Hwang JW, Jung HS, Lee DY (2011) Inhibition of platelet adhesion onto intrahepatically transplanted islets using PEGylation for attenuating instant blood-mediated inflammatory reaction (IBMIR). J Control Release 152(Suppl 1):e213–e214

    Article  CAS  PubMed  Google Scholar 

  66. Teramura Y, Iwata H (2011) Improvement of graft survival by surface modification with poly(ethylene glycol)-lipid and urokinase in intraportal islet transplantation. Transplantation 91(3):271–278

    Article  CAS  PubMed  Google Scholar 

  67. Luan NM, Teramura Y, Iwata H (2011) Immobilization of soluble complement receptor 1 on islets. Biomaterials 32(20):4539–4545

    Article  CAS  PubMed  Google Scholar 

  68. Luan NM, Teramura Y, Iwata H (2011) Layer-by-layer co-immobilization of soluble complement receptor 1 and heparin on islets. Biomaterials 32(27):6487–6492

    Article  PubMed  Google Scholar 

  69. Chen H, Teramura Y, Iwata H (2011) Co-immobilization of urokinase and thrombomodulin on islet surfaces by poly(ethylene glycol)-conjugated phospholipid. J Control Release 150(2):229–234

    Article  CAS  PubMed  Google Scholar 

  70. Teramura Y, Iwata H (2009) Surface modification of islets with PEG-lipid for improvement of graft survival in intraportal transplantation. Transplantation 88(5):624–630

    Article  PubMed  Google Scholar 

  71. Im BH, Jeong JH, Haque MR, Lee DY, Ahn CH, Kim JE, Byun Y (2013) The effects of 8-arm-PEG-catechol/heparin shielding system and immunosuppressive drug, FK506 on the survival of intraportally allotransplanted islets. Biomaterials 34(8):2098–2106

    Article  CAS  PubMed  Google Scholar 

  72. Hilbrands R, Huurman VA, Gillard P, Velthuis JH, De Waele M, Mathieu C, Kaufman L, Pipeleers-Marichal M, Ling Z, Movahedi B, Jacobs-Tulleneers-Thevissen D, Monbaliu D, Ysebaert D, Gorus FK, Roep BO, Pipeleers DG, Keymeulen B (2009) Differences in baseline lymphocyte counts and autoreactivity are associated with differences in outcome of islet cell transplantation in type 1 diabetic patients. Diabetes 58(10):2267–2276

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  73. Harlan DM, Kenyon NS, Korsgren O, Roep BO (2009) Current advances and travails in islet transplantation. Diabetes 58(10):2175–2184

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  74. Calafiore R, Basta G, Luca G, Lemmi A, Racanicchi L, Mancuso F, Montanucci MP, Brunetti P (2006) Standard technical procedures for microencapsulation of human islets for graft into nonimmunosuppressed patients with type 1 diabetes mellitus. Transplant Proc 38(4):1156–1157

    Article  CAS  PubMed  Google Scholar 

  75. O’Sullivan ES, Vegas A, Anderson DG, Weir GC (2011) Islets transplanted in immunoisolation devices: a review of the progress and the challenges that remain. Endocr Rev 32(6):827–844

    Article  PubMed Central  PubMed  Google Scholar 

  76. Pierson RN 3rd (2009) Antibody-mediated xenograft injury: mechanisms and protective strategies. Transpl Immunol 21(2):65–69

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  77. Kirchhof N, Shibata S, Wijkstrom M, Kulick DM, Salerno CT, Clemmings SM, Heremans Y, Galili U, Sutherland DE, Dalmasso AP, Hering BJ (2004) Reversal of diabetes in non-immunosuppressed rhesus macaques by intraportal porcine islet xenografts precedes acute cellular rejection. Xenotransplantation 11(5):396–407

    Article  PubMed  Google Scholar 

  78. Soderlund J, Wennberg L, Castanos-Velez E, Biberfeld P, Zhu S, Tibell A, Groth CG, Korsgren O (1999) Fetal porcine islet-like cell clusters transplanted to cynomolgus monkeys: an immunohistochemical study. Transplantation 67(6):784–791

    Article  CAS  PubMed  Google Scholar 

  79. de Vos P, Marchetti P (2002) Encapsulation of pancreatic islets for transplantation in diabetes: the untouchable islets. Trends Mol Med 8(8):363–366

    Article  PubMed  Google Scholar 

  80. Klymiuk N, van Buerck L, Bahr A, Offers M, Kessler B, Wuensch A, Kurome M, Thormann M, Lochner K, Nagashima H, Herbach N, Wanke R, Seissler J, Wolf E (2012) Xenografted islet cell clusters from INSLEA29Y transgenic pigs rescue diabetes and prevent immune rejection in humanized mice. Diabetes 61(6):1527–1532

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  81. Henquin JC (2000) Triggering and amplifying pathways of regulation of insulin secretion by glucose. Diabetes 49(11):1751–1760

    Article  CAS  PubMed  Google Scholar 

  82. Hellman B, Gylfe E, Bergsten P, Grapengiesser E, Lund PE, Berts A, Tengholm A, Pipeleers DG, Ling Z (1994) Glucose induces oscillatory Ca2+ signalling and insulin release in human pancreatic beta cells. Diabetologia 37(Suppl 2):S11–S20

    Article  CAS  PubMed  Google Scholar 

  83. Marchetti P, Scharp DW, McLear M, Gingerich R, Finke E, Olack B, Swanson C, Giannarelli R, Navalesi R, Lacy PE (1994) Pulsatile insulin secretion from isolated human pancreatic islets. Diabetes 43(6):827–830

    Article  CAS  PubMed  Google Scholar 

  84. Buchwald P, Cechin SR, Weaver JD, Stabler CL (2015) Experimental evaluation and computational modeling of the effects of encapsulation on the time-profile of glucose-stimulated insulin release of pancreatic islets. Biomed Eng Online 14(1):28

    Article  PubMed Central  PubMed  Google Scholar 

  85. Blasi P, Luca G, Mancuso F, Schoubben A, Calvitti M, Giovagnoli S, Basta G, Becchetti E, Ricci M, Calafiore R (2013) Conformal polymer coatings for pancreatic islets transplantation. Int J Pharm 440(2):141–147

    Article  CAS  PubMed  Google Scholar 

  86. Orive G, Hernandez RM, Gascon AR, Calafiore R, Chang TM, De Vos P, Hortelano G, Hunkeler D, Lacik I, Shapiro AM, Pedraz JL (2003) Cell encapsulation: promise and progress. Nat Med 9(1):104–107

    Article  CAS  PubMed  Google Scholar 

  87. Orive G, Gascon AR, Hernandez RM, Igartua M, Luis Pedraz J (2003) Cell microencapsulation technology for biomedical purposes: novel insights and challenges. Trends Pharmacol Sci 24(5):207–210

    Article  CAS  PubMed  Google Scholar 

  88. de Vos P, Hamel AF, Tatarkiewicz K (2002) Considerations for successful transplantation of encapsulated pancreatic islets. Diabetologia 45(2):159–173

    Article  PubMed  Google Scholar 

  89. Vaithilingam V, Kollarikova G, Qi M, Lacik I, Oberholzer J, Guillemin GJ, Tuch BE (2011) Effect of prolonged gelling time on the intrinsic properties of barium alginate microcapsules and its biocompatibility. J Microencapsul 28(6):499–507

    Article  CAS  PubMed  Google Scholar 

  90. De Vos P, Vegter D, De Haan BJ, Strubbe JH, Bruggink JE, Van Schilfgaarde R (1996) Kinetics of intraperitoneally infused insulin in rats. Functional implications for the bioartificial pancreas. Diabetes 45(8):1102–1107

    Article  PubMed  Google Scholar 

  91. Yang HK,Yoon KH (2015) Current status of encapsulated islet transplantation. J Diabet Complications

  92. Pareta R, McQuilling JP, Sittadjody S, Jenkins R, Bowden S, Orlando G, Farney AC, Brey EM, Opara EC (2014) Long-term function of islets encapsulated in a redesigned alginate microcapsule construct in omentum pouches of immune-competent diabetic rats. Pancreas 43(4):605–613

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  93. Juang JH, Bonner-Weir S, Ogawa Y, Vacanti JP, Weir GC (1996) Outcome of subcutaneous islet transplantation improved by polymer device. Transplantation 61(11):1557–1561

    Article  CAS  PubMed  Google Scholar 

  94. De Vos P, Hillebrands JL, De Haan BJ, Strubbe JH, Van Schilfgaarde R (1997) Efficacy of a prevascularized expanded polytetrafluoroethylene solid support system as a transplantation site for pancreatic islets. Transplantation 63(6):824–830

    Article  PubMed  Google Scholar 

  95. Eberhard D, Kragl M, Lammert E (2010) ‘Giving and taking’: endothelial and beta-cells in the islets of Langerhans. Trends Endocrinol Metab 21(8):457–463

    Article  CAS  PubMed  Google Scholar 

  96. Lammert E, Cleaver O, Melton D (2001) Induction of pancreatic differentiation by signals from blood vessels. Science 294(5542):564–567

    Article  CAS  PubMed  Google Scholar 

  97. Denner J,Graham M (2015) Xenotransplantation of islet cells: what can the non-human primate model bring for the evaluation of efficacy and safety? Xenotransplantation

  98. Graham ML, Bellin MD, Papas KK, Hering BJ, Schuurman HJ (2011) Species incompatibilities in the pig-to-macaque islet xenotransplant model affect transplant outcome: a comparison with allotransplantation. Xenotransplantation 18(6):328–342

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by the University Hospital Carl Gustav Carus, Department of Medicine III, and Paul Langerhans Institute Dresden of Helmholtz Centre Munich at University Clinic Carl Gustav Carus of TU Dresden Faculty of Medicine, Technische Universität Dresden, DZD- German Centre for Diabetes Research and by grants from the Deutsche Forschungsgemeinschaft SFB/TR127 (to B.L.).

Conflicts of interest

The authors declare that they have no conflict of interest.

Compliance with ethical standards

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

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Barbara Ludwig.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ludwig, B., Ludwig, S. Transplantable bioartificial pancreas devices: current status and future prospects. Langenbecks Arch Surg 400, 531–540 (2015). https://doi.org/10.1007/s00423-015-1314-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00423-015-1314-y

Keywords

Navigation