Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Alginate encapsulation as long-term immune protection of allogeneic pancreatic islet cells transplanted into the omental bursa of macaques

Nature Biomedical Engineering volume 2, pages 810–821 (2018)Cite this article

Subjects

Abstract

The transplantation of pancreatic islet cells could restore glycaemic control in patients with type 1 diabetes. Microspheres for islet encapsulation have enabled long-term glycaemic control in rodent models of diabetes; however, humans transplanted with equivalent microsphere formulations have experienced only transient islet graft function owing to a vigorous foreign-body response (FBR), to pericapsular fibrotic overgrowth (PFO) and, in upright bipedal species, to the sedimentation of the microspheres within the peritoneal cavity. Here, we report the results of the testing in non-human primate (NHP) models of seven alginate formulations that were efficacious in rodents, including three that led to transient islet graft function in clinical trials. All formulations elicited significant FBR and PFO 1 month post implantation; however, three chemically modified, immune-modulating alginate formulations elicited a reduced FBR. In conjunction with a minimally invasive transplantation technique into the bursa omentalis of NHPs, the most promising chemically modified alginate derivative (Z1-Y15) protected viable and glucose-responsive allogeneic islets for 4 months without the need for immunosuppression. Chemically modified alginate formulations may enable the long-term transplantation of islets for the correction of insulin deficiency.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Empty alginate spheres used in clinical trials induce FBRs and PFO post implantation in NHPs.
Fig. 2: Transplantation method causes differential spatial distribution of alginate spheres post implantation.
Fig. 3: Z1-Y15 alginate protects viable and glucose-responsive allogeneic islets in NHPs without any immunosuppression.

Similar content being viewed by others

References

  1. Chang, T. M. Semipermeable microcapsules. Science 146, 524–525 (1964).

    Article  CAS  Google Scholar 

  2. Lim, F. & Sun, A. M. Microencapsulated islets as bioartificial endocrine pancreas. Science 210, 908–910 (1980).

    Article  CAS  Google Scholar 

  3. Strand, B. L., Coron, A. E. & Skjak-Braek, G. Current and future perspectives on alginate encapsulated pancreatic islet. Stem Cells Transl. Med. 6, 1053–1058 (2017).

    Article  CAS  Google Scholar 

  4. Haug, A. & Smidsrod, O. Selectivity of some anionic polymers for divalent metal ions. Acta Chem. Scand. 24, 843 (1970).

    Article  CAS  Google Scholar 

  5. Kollmer, M., Appel, A. A., Somo, S. I. & Brey, E. M. Long-term function of alginate-encapsulated islets. Tissue Eng. Part B Rev. 22, 34–46 (2015).

    Article  Google Scholar 

  6. Mooranian, A., Negrulj, R., Arfuso, F. & Al-Salami, H. Characterization of a novel bile acid-based delivery platform for microencapsulated pancreatic beta-cells. Artif. Cells Nanomed. Biotechnol. 44, 194–200 (2016).

    Article  CAS  Google Scholar 

  7. Kleinberger, R. M., Burke, N. A., Zhou, C. & Stover, H. D. Synthetic polycations with controlled charge density and molecular weight as building blocks for biomaterials. J. Biomater. Sci. Polym. Ed. 27, 351–369 (2016).

    Article  CAS  Google Scholar 

  8. Duvivier-Kali, V. F., Omer, A., Lopez-Avalos, M. D., O’Neil, J. J. & Weir, G. C. Survival of microencapsulated adult pig islets in mice in spite of an antibody response. Am. J. Transplant. 4, 1991–2000 (2004).

    Article  CAS  Google Scholar 

  9. Duvivier-Kali, V. F., Omer, A., Parent, R. J., O’Neil, J. J. & Weir, G. C. Complete protection of islets against allorejection and autoimmunity by a simple barium-alginate membrane. Diabetes 50, 1698–1705 (2001).

    Article  CAS  Google Scholar 

  10. Omer, A. et al. Long-term normoglycemia in rats receiving transplants with encapsulated islets. Transplantation 79, 52–58 (2005).

    Article  CAS  Google Scholar 

  11. Dolgin, E. Diabetes: encapsulating the problem. Nature 540, S60–S62 (2016).

    Article  CAS  Google Scholar 

  12. Basta, G. et al. Long-term metabolic and immunological follow-up of nonimmunosuppressed patients with type 1 diabetes treated with microencapsulated islet allografts: four cases. Diabetes Care 34, 2406–2409 (2011).

    Article  CAS  Google Scholar 

  13. Calafiore, R. et al. Microencapsulated pancreatic islet allografts into nonimmunosuppressed patients with type 1 diabetes: first two cases. Diabetes Care 29, 137–138 (2006).

    Article  Google Scholar 

  14. Tuch, B. E. et al. Safety and viability of microencapsulated human islets transplanted into diabetic humans. Diabetes Care 32, 1887–1889 (2009).

    Article  CAS  Google Scholar 

  15. Jacobs-Tulleneers-Thevissen, D. et al. Sustained function of alginate-encapsulated human islet cell implants in the peritoneal cavity of mice leading to a pilot study in a type 1 diabetic patient. Diabetologia 56, 1605–1614 (2013).

    Article  CAS  Google Scholar 

  16. O’Sullivan, E. S., Vegas, A., Anderson, D. G. & Weir, G. C. Islets transplanted in immunoisolation devices: a review of the progress and the challenges that remain. Endocr. Rev. 32, 827–844 (2011).

    Article  Google Scholar 

  17. Qi, M. et al. A recommended laparoscopic procedure for implantation of microcapsules in the peritoneal cavity of non-human primates. J. Surg. Res. 168, e117–e123 (2011).

    Article  Google Scholar 

  18. de Vos, P., Hamel, A. F. & Tatarkiewicz, K. Considerations for successful transplantation of encapsulated pancreatic islets. Diabetologia 45, 159–173 (2002).

    Article  Google Scholar 

  19. Vaithilingam, V. & Tuch, B. E. Islet transplantation and encapsulation: an update on recent developments. Rev. Diabet. Stud. 8, 51–67 (2011).

    Article  Google Scholar 

  20. Desai, T. & Shea, L. D. Advances in islet encapsulation technologies. Nat. Rev. Drug Discov. 16, 338–350 (2017); erratum 16, 367 (2017).

    Article  CAS  Google Scholar 

  21. Doloff, J. C. et al. Colony stimulating factor-1 receptor is a central component of the foreign body response to biomaterial implants in rodents and non-human primates. Nat. Mater. 16, 671–680 (2017).

    Article  CAS  Google Scholar 

  22. King, A., Sandler, S. & Andersson, A. The effect of host factors and capsule composition on the cellular overgrowth on implanted alginate capsules. J. Biomed. Mater. Res. 57, 374–383 (2001).

    Article  CAS  Google Scholar 

  23. Phillips, K. A. et al. Why primate models matter. Am. J. Primatol. 76, 801–827 (2014).

    Article  Google Scholar 

  24. Mestas, J. & Hughes, C. C. Of mice and not men: differences between mouse and human immunology. J. Immunol. 172, 2731–2738 (2004).

    Article  CAS  Google Scholar 

  25. Messaoudi, I., Estep, R., Robinson, B. & Wong, S. W. Nonhuman primate models of human immunology. Antioxid. Redox Signal. 14, 261–273 (2011).

    Article  CAS  Google Scholar 

  26. Vegas, A. J. et al. Combinatorial hydrogel library enables identification of materials that mitigate the foreign body response in primates. Nat. Biotechnol. 34, 345–352 (2016).

    Article  CAS  Google Scholar 

  27. Veiseh, O. et al. Size- and shape-dependent foreign body immune response to materials implanted in rodents and non-human primates. Nat. Mater. 14, 643–651 (2015).

    Article  CAS  Google Scholar 

  28. Morch, Y. A., Donati, I., Strand, B. L. & Skjak-Braek, G. Effect of Ca2+, Ba2+, and Sr2+ on alginate microbeads. Biomacromolecules 7, 1471–1480 (2006).

    Article  CAS  Google Scholar 

  29. Qi, M. et al. Encapsulation of human islets in novel inhomogeneous alginate-Ca2+/Ba2+ microbeads: in vitro and in vivo function. Artif. Cells Blood Substit. Immobil. Biotechnol. 36, 403–420 (2008).

    Article  CAS  Google Scholar 

  30. Morch, Y. A. et al. Binding and leakage of barium in alginate microbeads. J. Biomed. Mater. Res. A 100, 2939–2947 (2012).

    Article  Google Scholar 

  31. Rokstad, A. M., Lacik, I., de Vos, P. & Strand, B. L. Advances in biocompatibility and physico-chemical characterization of microspheres for cell encapsulation. Adv. Drug Deliv. Rev. 67–68, 111–130 (2014).

    Article  Google Scholar 

  32. Anderson, J. M., Rodriguez, A. & Chang, D. T. Foreign body reaction to biomaterials. Semin. Immunol. 20, 86–100 (2008).

    Article  CAS  Google Scholar 

  33. Kolb, M. et al. Differences in the fibrogenic response after transfer of active transforming growth factor-beta1 gene to lungs of “fibrosis-prone” and “fibrosis-resistant” mouse strains. Am. J. Respir. Cell Mol. Biol. 27, 141–150 (2002).

    Article  CAS  Google Scholar 

  34. Vegas, A. J. et al. Long-term glycemic control using polymer-encapsulated human stem cell-derived beta cells in immune-competent mice. Nat. Med. 22, 306–311 (2016).

    Article  CAS  Google Scholar 

  35. Towell, M. E., Lysak, I., Layne, E. C. & Bessman, S. P. Tissue oxygen tension in rabbits measured with a galvanic electrode. J. Appl. Physiol. 41, 245–250 (1976).

    Article  CAS  Google Scholar 

  36. Klossner, J., Kivisaari, J. & Niinikoski, J. Oxygen and carbon dioxide tensions in the abdominal cavity and colonic wall of the rabbit. Am. J. Surg. 127, 711–715 (1974).

    Article  CAS  Google Scholar 

  37. Goh, F., Long, R. Jr, Simpson, N. & Sambanis, A. Dual perfluorocarbon method to noninvasively monitor dissolved oxygen concentration in tissue engineered constructs in vitro and in vivo. Biotechnol. Prog. 27, 1115–1125 (2011).

    Article  CAS  Google Scholar 

  38. Christoffersson, G. et al. Clinical and experimental pancreatic islet transplantation to striated muscle: establishment of a vascular system similar to that in native islets. Diabetes 59, 2569–2578 (2010).

    Article  CAS  Google Scholar 

  39. Toso, C. et al. Effect of microcapsule composition and short-term immunosuppression on intraportal biocompatibility. Cell Transplant. 14, 159–167 (2005).

    Article  Google Scholar 

  40. Dufrane, D. et al. The influence of implantation site on the biocompatibility and survival of alginate encapsulated pig islets in rats. Biomaterials 27, 3201–3208 (2006).

    Article  CAS  Google Scholar 

  41. Veriter, S. et al. In vivo selection of biocompatible alginates for islet encapsulation and subcutaneous transplantation. Tissue Eng. Part A 16, 1503–1513 (2010).

    Article  CAS  Google Scholar 

  42. Liu, X. Y., Nothias, J. M., Scavone, A., Garfinkel, M. & Millis, J. M. Biocompatibility investigation of polyethylene glycol and alginate-poly-L-lysine for islet encapsulation. ASAIO J. 56, 241–245 (2010).

    Article  CAS  Google Scholar 

  43. Yang, K. C. et al. Comparison of bioartificial pancreas performance in the bone marrow cavity and intramuscular space. Arch. Med. Res. 41, 151–153 (2010).

    Article  CAS  Google Scholar 

  44. Kobayashi, T. et al. Survival of microencapsulated islets at 400 days posttransplantation in the omental pouch of NOD mice. Cell Transplant. 15, 359–365 (2006).

    Article  Google Scholar 

  45. Pareta, R. et al. Long-term function of islets encapsulated in a redesigned alginate microcapsule construct in omentum pouches of immune-competent diabetic rats. Pancreas 43, 605–613 (2014).

    Article  CAS  Google Scholar 

  46. Robles, L., Storrs, R., Lamb, M., Alexander, M. & Lakey, J. R. Current status of islet encapsulation. Cell Transplant. 23, 1321–1348 (2014).

    Article  Google Scholar 

  47. Zhu, H. et al. Selection of implantation sites for transplantation of encapsulated pancreatic islets. Tissue Eng. Part B Rev. 24, 191–214 (2018).

    Article  Google Scholar 

  48. Pepper, A. R. et al. A prevascularized subcutaneous device-less site for islet and cellular transplantation. Nat. Biotechnol. 33, 518–523 (2015).

    Article  CAS  Google Scholar 

  49. Stokes, R. A. et al. Transplantation sites for human and murine islets. Diabetologia 60, 1961–1971 (2017).

    Article  CAS  Google Scholar 

  50. Olsson, R. & Carlsson, P. O. A low-oxygenated subpopulation of pancreatic islets constitutes a functional reserve of endocrine cells. Diabetes 60, 2068–2075 (2011).

    Article  CAS  Google Scholar 

  51. Avgoustiniatos, E. S. & Colton, C. K. Effect of external oxygen mass transfer resistances on viability of immunoisolated tissue. Ann. NY Acad. Sci. 831, 145–167 (1997).

    Article  CAS  Google Scholar 

  52. Nourmohammadzadeh, M. et al. Microfluidic array with integrated oxygenation control for real-time live-cell imaging: effect of hypoxia on physiology of microencapsulated pancreatic islets. Anal. Chem. 85, 11240–11249 (2013).

    Article  CAS  Google Scholar 

  53. Kim, W. H. et al. Exposure to chronic high glucose induces beta-cell apoptosis through decreased interaction of glucokinase with mitochondria: downregulation of glucokinase in pancreatic beta-cells. Diabetes 54, 2602–2611 (2005).

    Article  CAS  Google Scholar 

  54. Biarnes, M. et al. β-cell death and mass in syngeneically transplanted islets exposed to short- and long-term hyperglycemia. Diabetes 51, 66–72 (2002).

    Article  CAS  Google Scholar 

  55. Vallabhajosyula, P. et al. Effect of the diabetic state on islet engraftment and function in a large animal model of islet-kidney transplantation. Cell Transplant. 26, 1755–1762 (2017).

    Article  Google Scholar 

  56. Mueller, K. R. et al. Differences in glucose-stimulated insulin secretion in vitro of islets from human, nonhuman primate, and porcine origin. Xenotransplantation 20, 75–81 (2013).

    Article  Google Scholar 

  57. Qi, M. et al. Implementation of a simplified method of islet isolation for allogeneic islet transplantation in cynomolgus monkeys. Pancreas 43, 226–235 (2014).

    Article  CAS  Google Scholar 

  58. Qi, M. et al. Five-year follow-up of patients with type 1 diabetes transplanted with allogeneic islets: the UIC experience. Acta Diabetol. 51, 833–843 (2014).

    Article  CAS  Google Scholar 

  59. Gangemi, A. et al. Islet transplantation for brittle type 1 diabetes: the UIC protocol. Am. J. Transplant. 8, 1250–1261 (2008).

    Article  CAS  Google Scholar 

  60. Adewola, A. F. et al. Microfluidic perifusion and imaging device for multi-parametric islet function assessment. Biomed. Microdevices 12, 409–417 (2010).

    Article  Google Scholar 

  61. Keizer, J. & Magnus, G. ATP-sensitive potassium channel and bursting in the pancreatic beta cell. A theoretical study. Biophys. J. 56, 229–242 (1989).

    Article  CAS  Google Scholar 

  62. Klingberg, F., Hinz, B. & White, E. S. The myofibroblast matrix: implications for tissue repair and fibrosis. J. Pathol. 229, 298–309 (2013).

    Article  CAS  Google Scholar 

  63. Sheikh, Z., Brooks, P. J., Barzilay, O., Fine, N. & Glogauer, M. Macrophages, foreign body giant cells and their response to implantable biomaterials. Materials 8, 5671–5701 (2015).

    Article  CAS  Google Scholar 

  64. Wynn, T. A. & Vannella, K. M. Macrophages in tissue repair, regeneration, and fibrosis. Immunity 44, 450–462 (2016).

    Article  CAS  Google Scholar 

  65. Mantovani, A., Biswas, S. K., Galdiero, M. R., Sica, A. & Locati, M. Macrophage plasticity and polarization in tissue repair and remodelling. J. Pathol. 229, 176–185 (2013).

    Article  CAS  Google Scholar 

  66. Vaithilingam, V. et al. Beneficial effects of coating alginate microcapsules with macromolecular heparin conjugates-in vitro and in vivo study. Tissue Eng. Part A 20, 324–334 (2014).

    Article  CAS  Google Scholar 

  67. Kayaalp, C. Bursectomy at radical gastrectomy. World J. Gastrointest. Surg. 7, 249–253 (2015).

    Article  Google Scholar 

Download references

Acknowledgements

This work was supported jointly by the Chicago Diabetes Project and the JDRF and the Leona M. and Harry B. Helmsley Charitable Trust (grant number 3-SRA-2014-285-M-R (R.L. and D.G.A.)), the US National Institutes of Health (grant numbers DK091526 (J.O.) EB000244 (R.L.), EB000351 (R.L.), DE013023 (R.L.), CA151884 (R.L.) and UC4DK104218 (D.L.G.)), and through a gift from the Tayebati Family Foundation (D.G.A. and R.L.). This work was also supported by the Slovak Research and Development Agency under contract number APVV-14-858 (I.L.). O.V. was supported by JDRF and Department of Defense Congressionally Directed Medical Research Program (DOD/CDMRP) postdoctoral fellowships (grant numbers 3-2013-178 and W81XWH-13-1-0215, respectively). J.C.D. was supported by a JDRF postdoctoral fellowship (grant number 3-PDF-2015-91-A-N). The authors acknowledge L. Halliday and the veterinary staff at the Biological Resource Laboratories at UIC for their assistance and technical support during the course of the studies. We thank R. Calafiore and G. Basta from the University of Perugia for producing the A-PLO-A spheres under current good manufacturing practice conditions at the University of Illinois at Chicago for the herein described experiments. We thank B. Tuch and his team at the Diabetes Transplant Unit, Prince of Wales Hospital, Sydney, Australia, for the production of the UPMVG-Ba2+ spheres and sharing his experience from the clinical trials in encapsulated islet transplant trials conducted in Sydney, Australia. We thank H. H. Tam for his advice on the statistical analysis of datasets.

Author information

Author notes

  1. Omid Veiseh, Jie Li & Karsten Olejnik

    Present address: Department of Bioengineering, Rice University, Houston, TX, USA

  2. Arturo J. Vegas

    Present address: Chemistry Department, Boston University, Boston, MA, USA

  3. James J. McGarrigle, Douglas Isa & Sofia Ghani

    Present address: CellTrans Inc., Chicago, IL, USA

  4. Mohammad Nourmohammadzadeh

    Present address: Department of Chemical and Biomolecular Engineering, North Carolina State University, Raleigh, NC, USA

  5. Yuan Xing, Yong Wang & Jose Oberholzer

    Present address: Department of Surgery and Biomedical Engineering, University of Virginia, Charlottesville, VA, USA

  6. These authors contributed equally to this work: Matthew A. Bochenek, Omid Veiseh.

Authors and Affiliations

  1. Division of Transplantation, Department of Surgery, University of Illinois at Chicago, Chicago, IL, USA

    Matthew A. Bochenek, James J. McGarrigle, Meirigeng Qi, Enza Marchese, Mustafa Omami, Joshua Mendoza-Elias, Mohammad Nourmohammadzadeh, Arshad Khan, Chun-Chieh Yeh, Yuan Xing, Douglas Isa, Sofia Ghani, Yong Wang & Jose Oberholzer

  2. Department of Bioengineering, University of Illinois at Chicago, Chicago, IL, USA

    Matthew A. Bochenek, Joshua Mendoza-Elias, Mohammad Nourmohammadzadeh, Yuan Xing, Yong Wang & Jose Oberholzer

  3. David H Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA

    Matthew A. Bochenek, Omid Veiseh, Arturo J. Vegas, Joshua C. Doloff, Jie Li, Casey Landry, Andrew R. Bader, Karsten Olejnik, Michael Chen, Robert Langer & Daniel G. Anderson

  4. Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA

    Matthew A. Bochenek, Omid Veiseh, Arturo J. Vegas, Joshua C. Doloff, Jie Li, Casey Landry, Andrew R. Bader, Karsten Olejnik, Michael Chen, Robert Langer & Daniel G. Anderson

  5. Department of Anesthesiology, Boston Children’s Hospital, Boston, MA, USA

    Matthew A. Bochenek, Omid Veiseh, Arturo J. Vegas, Joshua C. Doloff, Jie Li, Casey Landry, Andrew R. Bader, Karsten Olejnik, Michael Chen, Robert Langer & Daniel G. Anderson

  6. Section on Islet Cell and Regenerative Biology, Research Division, Joslin Diabetes Center, Boston, MA, USA

    Jennifer Hollister-Lock & Gordon C. Weir

  7. Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, USA

    Dale L. Greiner

  8. Department of Biotechnology and Food Sciences, Norwegian University of Science and Technology, Trondheim, Norway

    Berit Løkensgard Strand

  9. Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway

    Anne Mari A. Rokstad

  10. Centre of Obesity, Clinic of Surgery, St. Olavs University Hospital, Trondheim, Norway

    Anne Mari A. Rokstad

  11. Polymer Institute, Slovak Academy of Sciences, Bratislava, Slovakia

    Igor Lacik

  12. Howard Hughes Medical Institute, Harvard University, Cambridge, MA, USA

    Robert Langer & Daniel G. Anderson

  13. Division of Health Science Technology, Massachusetts Institute of Technology, Cambridge, MA, USA

    Robert Langer & Daniel G. Anderson

  14. Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA, USA

    Robert Langer & Daniel G. Anderson

  15. Sigilon Therapeutics, Inc., Cambridge, MA, USA

    Omid Veiseh, Jie Li & Karsten Olejnik

Authors
  1. Matthew A. Bochenek
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Omid Veiseh
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Arturo J. Vegas
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. James J. McGarrigle
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Meirigeng Qi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Enza Marchese
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Mustafa Omami
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Joshua C. Doloff
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Joshua Mendoza-Elias
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Mohammad Nourmohammadzadeh
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Arshad Khan
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Chun-Chieh Yeh
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Yuan Xing
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Douglas Isa
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Sofia Ghani
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Jie Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Casey Landry
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Andrew R. Bader
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. Karsten Olejnik
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. Michael Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  21. Jennifer Hollister-Lock
    View author publications

    You can also search for this author in PubMed Google Scholar

  22. Yong Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  23. Dale L. Greiner
    View author publications

    You can also search for this author in PubMed Google Scholar

  24. Gordon C. Weir
    View author publications

    You can also search for this author in PubMed Google Scholar

  25. Berit Løkensgard Strand
    View author publications

    You can also search for this author in PubMed Google Scholar

  26. Anne Mari A. Rokstad
    View author publications

    You can also search for this author in PubMed Google Scholar

  27. Igor Lacik
    View author publications

    You can also search for this author in PubMed Google Scholar

  28. Robert Langer
    View author publications

    You can also search for this author in PubMed Google Scholar

  29. Daniel G. Anderson
    View author publications

    You can also search for this author in PubMed Google Scholar

  30. Jose Oberholzer
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

M.A.B., O.V., A.J.V., J.J.M., D.G.A. and J.O. designed the experiments, analysed the data and wrote the manuscript. M.A.B., O.V., A.J.V., J.J.M., M.Q., E.M., M.O., J.C.D., J.M.-E., M.N., A.K., C.-C.Y., Y.X., D.I., S.G., J.L., C.L., A.R.B., K.O., M.C., Y.W. and J.O. performed experiments. J.H.-L., D.L.G., G.C.W., B.L.S., A.M.A.R., I.L. and R.L. provided conceptual advice and technical support. R.L., D.G.A. and J.O. supervised the study. All of the authors discussed the results and assisted in the preparation of the manuscript.

Corresponding authors

Correspondence to Daniel G. Anderson or Jose Oberholzer.

Ethics declarations

Competing interests

O.V., A.J.V., R.L., D.G.A. and J.O. are founding scientists of Sigilon Therapeutics, a biotech company based in Cambridge, MA, USA, that produces antifibrotic materials for cell-based therapies. J.O. is founder and President of CellTrans, a biotech company based in Chicago, IL, USA, for the transplantation of cell-based therapies.

Additional information

Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Supplementary Information

Supplementary figures and tables

Reporting Summary

Supplementary Video 1

Non-invasive laparoscopic transplantation technique for hydrogel spheres into the bursa omentalis

Supplementary Video 2

Non-invasive laparoscopic retrieval of Z1-Y15 spheres containing allogeneic islets performed 1-month post-transplantation

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bochenek, M.A., Veiseh, O., Vegas, A.J. et al. Alginate encapsulation as long-term immune protection of allogeneic pancreatic islet cells transplanted into the omental bursa of macaques. Nat Biomed Eng 2, 810–821 (2018). https://doi.org/10.1038/s41551-018-0275-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41551-018-0275-1

This article is cited by

Search

Advanced search

Quick links

Nature Briefing: Translational Research

Sign up for the Nature Briefing: Translational Research newsletter — top stories in biotechnology, drug discovery and pharma.

Get what matters in translational research, free to your inbox weekly. Sign up for Nature Briefing: Translational Research