Skip to main content

Pig-to-Macaque Islet Xenotransplantation

  • Protocol
  • First Online:
Xenotransplantation

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2110))

Abstract

The advancement toward a clinical application for porcine islets to cure diabetes in humans must include reproducible long-term successes in non-human primate (NHP) models. Many dedicated researchers around the world are continuing to work toward this goal. In this chapter, we describe procedures for islet isolation of pancreatic islets from adult and neonatal/fetal pigs. We further include procedures for the induction of diabetes in non-human primates and subsequent insulin therapy, islet transplantation, immunosuppression, and also the daily maintenance of xenotransplanted NHPs. The procedures that we outline in this chapter are ones that we have successfully utilized in pig-to-NHP islet transplantation models. However, where appropriate, alternative methods will also be identified.

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

Access this chapter

Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Sutherland DE, Gruessner AC, Gruessner RW (1998) Pancreas transplantation: a review. Transplant Proc 30(5):1940–1943

    Article  CAS  Google Scholar 

  2. Moassesfar S, Masharani U, Frassetto LA et al (2016) A comparative analysis of the safety, efficacy, and cost of islet versus pancreas transplantation in nonuremic patients with type 1 diabetes. Am J Transplant 16(2):518–526

    Article  CAS  Google Scholar 

  3. 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(4):230–238

    Article  CAS  Google Scholar 

  4. Ryan EA, Paty BW, Senior PA et al (2005) Five-year follow-up after clinical islet transplantation. Diabetes 54(7):2060–2069

    Article  CAS  Google Scholar 

  5. Foster ED, Bridges ND, Feurer ID et al (2018) Improved health-related quality of life in a phase 3 islet transplantation trial in type 1 diabetes complicated by severe hypoglycemia. Diabetes Care 41(5):1001–1008

    Article  Google Scholar 

  6. Fiorina P, Shapiro AM, Ricordi C, Secchi A (2008) The clinical impact of islet transplantation. Am J Transplant 8(10):1990–1997

    Article  CAS  Google Scholar 

  7. Thompson DM, Meloche M, Ao Z et al (2011) Reduced progression of diabetic microvascular complications with islet cell transplantation compared with intensive medical therapy. Transplantation 91(3):373–378

    Article  Google Scholar 

  8. van der Windt DJ, Bottino R, Kumar G et al (2012) Clinical islet xenotransplantation: how close are we? Diabetes 61(12):3046–3055

    Article  Google Scholar 

  9. Nagaraju S, Bottino R, Wijkstrom M, Trucco M, Cooper DKC (2015) Islet xenotransplantation: what is the optimal age of the islet-source pig? Xenotransplantation 22:7–19

    Article  Google Scholar 

  10. Prabhakaran S, Hering BJ (2008) What strain of pig should be used? Xenotransplantation 15:83–86

    Article  Google Scholar 

  11. Liu Z, Hu W, He T et al (2017) Pig-to primate islet xenotransplantation: past, present, and future. Cell Transplant 26(6):925–947

    Article  Google Scholar 

  12. Park CG, Bottino R, Hawthorne WJ (2015) Current status of islet xenotransplantation. Int J Surg 23(Pt B):261–266

    Article  Google Scholar 

  13. Bottino R, Wijkstrom M, van der Windt DJ et al (2014) Pig-to-monkey islet xenotransplantation using multi-transgenic pigs. Am J Transplant 14(10):2275–2287

    Article  CAS  Google Scholar 

  14. van der Windt DJ, Bottino R, Casu A et al (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  Google Scholar 

  15. Korsgren O, Sandler S, Landström AS, Jansson L, Andersson A (1988) Large-scale production of fetal porcine pancreatic isletlike cell clusters. An experimental tool for studies of islet cell differentiation and xenotransplantation. Transplantation 45(3):509–514

    Article  CAS  Google Scholar 

  16. Korbutt GS, Elliott JF, Ao Z, Smith DK, Warnock GL, Rajotte RV (1996) Large scale isolation, growth, and function of porcine neonatal islet cells. J Clin Invest 97(9):2119–2129

    Article  CAS  Google Scholar 

  17. Trivedi N, Hollister-Lock J, Lopez-Avalos MD et al (2001) Increase in beta-cell mass in transplanted porcine neonatal pancreatic cell clusters is due to proliferation of beta-cells and differentiation of duct cells. Endocrinology 142(5):2115–2122

    Article  CAS  Google Scholar 

  18. 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(3):304–306

    Article  CAS  Google Scholar 

  19. Valdes-Gonzalez R, Rodriguez-Ventura AL, White DJG et al (2010) Long-term follow-up of patients with type 1 diabetes transplanted with neonatal pig islets. Clin Exp Immunol 162:537–542

    Article  CAS  Google Scholar 

  20. 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. Zong Nan Da Xue Xue Bao Yi Xue Ban 36(12):1134–1140

    CAS  Google Scholar 

  21. McNamee GA Jr, Wannemacher RW Jr, Dinterman RE, Rozmiarek H, Montrey RD (1984) A surgical procedure and tethering system for chronic blood sampling, infusion, and temperature monitoring in caged nonhuman primates. Lab Anim Sci 34(3):303–307

    PubMed  Google Scholar 

  22. Rood PP, Bottino R, Balamurugan AN et al (2006) Induction of diabetes in cynomolgus monkeys with high-dose streptozotocin: adverse effects and early responses. Pancreas 33(3):287–292

    Article  CAS  Google Scholar 

  23. Graham ML, Rieke EF, Dunning M et al (2009) A novel alternative placement site and technique for totally implantable vascular access ports in non-human primates. J Med Primatol 38(3):204–212

    Article  Google Scholar 

  24. Shin JS, Kim JM, Min BH et al (2018) Pre-clinical results in pig-to-non-human primate islet xenotransplantation using anti-CD40 antibody (2C10R4)-based immunosuppression. Xenotransplantation 25(1). https://doi.org/10.1111/xen.12356

  25. Bottino R, Knoll MF, Graeme-Wilson J et al (2017) Safe use of anti-CD154 monoclonal antibody in pig islet xenotransplantation in monkeys. Xenotransplantation 24(1). https://doi.org/10.1111/xen.12283

  26. Thompson P, Badell IR, Lowe M et al (2011) Islet xenotransplantation using gal-deficient neonatal donors improves engraftment and function. Am J Transplant 11(12):2593–2602

    Article  CAS  Google Scholar 

Download references

Acknowledgments

The authors kindly wish to recognize and thank Anna Lisa Haughwout for her splendid illustration of the primate tether system.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Rita Bottino .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2020 Springer Science+Business Media, LLC, part of Springer Nature

About this protocol

Check for updates. Verify currency and authenticity via CrossMark

Cite this protocol

Bertera, S., Knoll, M.F., Knoll, C.A., Cooper, D.K.C., Trucco, M., Bottino, R. (2020). Pig-to-Macaque Islet Xenotransplantation. In: Costa, C. (eds) Xenotransplantation. Methods in Molecular Biology, vol 2110. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-0255-3_19

Download citation

  • DOI: https://doi.org/10.1007/978-1-0716-0255-3_19

  • Published:

  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-0716-0254-6

  • Online ISBN: 978-1-0716-0255-3

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics