Skip to main content
SpringerLink
Log in

Xenogeneic Lung Transplantation Models

  • Protocol
  • First Online:
Xenotransplantation

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

Abstract

Study of lung xenografts has proven useful to understand the remaining barriers to successful transplantation of other organ xenografts. In this chapter, the history and current status of lung xenotransplantation will be briefly reviewed, and two different experimental models, the ex vivo porcine-to-human lung perfusion and the in vivo xenogeneic lung transplantation, will be presented. We will focus on the technical details of these lung xenograft models in sufficient detail, list the needed materials, and mention analysis techniques to allow others to adopt them with minimal learning curve.

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

Access this chapter

Log in via an institution
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. Pierson RN 3rd, Dorling A, Ayares D et al (2009) Current status of xenotransplantation and prospects for clinical application. Xenotransplantation 16:263–280

    Article  Google Scholar 

  2. Schroeder C, Allan JS, Nguyen BN et al (2005) Hyperacute rejection is attenuated in GalT knockout swine lungs perfused ex vivo with human blood. Transplant Proc 37:512–513

    Article  CAS  Google Scholar 

  3. Hisashi Y, Yamada K, Kuwaki K et al (2008) Rejection of cardiac xenografts transplanted from alpha1,3-galactosyltransferase gene-knockout (GalT-KO) pigs to baboons. Am J Transplant 8:2516–2526

    Article  CAS  Google Scholar 

  4. Burdorf L, Stoddard T, Zhang T et al (2014) GalTKO.hCD46 lung xenograft injury is associated with thrombin generation and platelet activation. Am J Transplant 14:1084–1095

    Article  CAS  Google Scholar 

  5. Burdorf L, Rybak E, Zhang T et al (2013) Human EPCR expression in GalTKO.hCD46 lungs extends survival time and lowers PVR in a xenogenic lung perfusion model. J Heart Lung Transplant 32:S137

    Article  Google Scholar 

  6. Bryant L, Eiseman B, Avery M (1968) Studies of the porcine lung as an oxygenator for human blood. J Thorac Cardiovasc Surg 55:255–263

    Article  Google Scholar 

  7. Collins BJ, Blum MG, Parker RE et al (2001) Thromboxane mediates pulmonary hypertension and lung inflammation during hyperacute lung rejection. J Appl Physiol 90:2257–2268

    Article  CAS  Google Scholar 

  8. Burdorf L, Harris D, Dahi S et al (2018) Thromboxane and histamine mediate PVR elevation during xenogeneic pig lung perfusion with human blood. Xenotransplantation 3:e12458

    Google Scholar 

  9. Cantu E, Balsara KR, Li B et al (2007) Prolonged function of macrophage, von Willebrand factor-deficient porcine pulmonary xenografts. Am J Transplant 7:66–75

    Article  CAS  Google Scholar 

  10. Schroeder C, Wu GS, Price E et al (2003) Hyperacute rejection of mouse lung by human blood: characterization of the model and the role of complement. Transplantation 76:755–760

    Article  CAS  Google Scholar 

  11. Komatsu K, Youm W, Konishi H et al (1996) Prolonged survival of hamster-to-rat pulmonary xenografts by tacrolimus (FK506) and cyclophosphamide. J Heart Lung Transplant 15:722–727

    CAS  PubMed  Google Scholar 

  12. Miyata Y, Ohdan H, Yoshioka S et al (1998) Relationship of xenogeneic microchimerism to graft outcome in hamster-to-rat lung xenotransplantation. J Heart Lung Transplant 17:233–240

    CAS  PubMed  Google Scholar 

  13. Nonaka M, Kadokura M, Kataoka D et al (2000) Hyperacute xenorejection of Guinea pig-to-rat lung transplantation can be attenuated by blood which has perfused another xenograft. Ann Thorac Cardiovasc Surg 6:146–150

    CAS  PubMed  Google Scholar 

  14. De Perrot M, Keshavjee S, Tabata T et al (2002) A simplified model for en bloc double lung xenotransplantation from hamster to rat. J Heart Lung Transplant 21:286–289

    Article  Google Scholar 

  15. Yang YG, deGoma E, Ohdan H et al (1998) Tolerization of anti-Galalpha1-3Gal natural antibody-forming B cells by induction of mixed chimerism. J Exp Med 187:1335–1342

    Article  CAS  Google Scholar 

  16. Veith FJ, Richards KU, Hagstrom JWC, Montefusco CM (1981) Intrafamilial lung xenograft from fox to dog. J Thorac Cardiovasc Surg 81:546–552

    Article  CAS  Google Scholar 

  17. Takeda M, Kawauchi M, Nakajima J, Furuse A (1995) Methotrexate in rescue therapy for xenotransplanted lung in primes. In: (Abstract po-46) Third International Congress of Xenotransplantation, Boston, 1995

    Google Scholar 

  18. Sadeghi AM, Laks H, Drinkwater DC et al (1991) Heart-lung xenotransplantation in primates. J Heart Lung Transplant 10:442–447

    CAS  PubMed  Google Scholar 

  19. Daggett CW, Yeatman M, Lodge AJ et al (1998) Total respiratory support from swine lungs in primate recipients. J Thorac Cardiovasc Surg 115:19–27

    Article  CAS  Google Scholar 

  20. Macchiarini P, Oriol R, Azimzadeh A et al (1999) Characterization of a pig-to-goat orthotopic lung xenotransplantation model to study beyond hyperacute rejection. J Thorac Cardiovasc Surg 118:805–814

    Article  CAS  Google Scholar 

  21. Sahara H, Watanabe H, Pomposelli T et al (2017) Lung xenotransplantation. Curr Opin Organ Transplant 22:541–548

    Article  Google Scholar 

  22. Burdorf L, Azimzadeh AM, Pierson RN III (2018) Progress and challenges in lung xenotransplantation: an update. Curr Opin Organ Transplant 23:621–627

    Article  CAS  Google Scholar 

  23. Sahara H, Sekijima M, Ariyoshi Y et al (2018) Effects of carbon monoxide on early dysfunction and microangiopathy following GalT-KO porcine pulmonary xenotransplantation in cynomolgus monkeys. Xenotransplantation 25(1). https://doi.org/10.1111/xen.12359

  24. Nguyen BN, Azimzadeh AM, Zhang T et al (2007) Life-supporting function of genetically modified swine lungs in baboons. J Thorac Cardiovasc Surg 133:1354–1363

    Article  Google Scholar 

  25. Yeatman M, Daggett CW, Parker W et al (1998) Complement-mediated pulmonary xenograft injury - studies in swine-to-primate orthotopic single lung transplant models. Transplantation 65:1084–1093

    Article  CAS  Google Scholar 

  26. Cantu E, Parker W, Platt JL, Duane Davis R (2004) Pulmonary xenotransplantation: rapidly progressing into the unknown. Am J Transplant 4(Suppl 6):25–35

    Article  CAS  Google Scholar 

  27. Harris DG, Quinn KJ, French BM et al (2015) Meta-analysis of the independent and cumulative effects of multiple genetic modifications on pig lung xenograft performance during ex vivo perfusion with human blood. Xenotransplantation 22:102–111

    Article  Google Scholar 

  28. Laird CT, Burdorf L, French BM et al (2017) Transgenic expression of human leukocyte antigen-E attenuates GalKO.hCD46 porcine lung xenograft injury. Xenotransplantation 24(2). https://doi.org/10.1111/xen.12294

  29. French BM, Sendil S, Sepuru KM et al (2018) Interleukin-8 mediates neutrophil-endothelial interactions in pig-to-human xenogeneic models. Xenotransplantation 25:e12385

    Article  Google Scholar 

  30. Burdorf L, Riner A, Rybak E et al (2016) Platelet sequestration and activation during GalTKO.hCD46 pig lung perfusion by human blood is primarily mediated by GPIb, GPIIb/IIIa, and von Willebrand Factor. Xenotransplantation 23:222–236

    Article  CAS  Google Scholar 

  31. Burdorf L, Laird C, Sendil S et al (2018) Progress in xenogeneic lung transplantation using multi-transgenic donor pigs and targeted supportive drug treatments. Transplantation 102:pS106

    Article  Google Scholar 

  32. Watanabe H, Sahara H, Nomura S et al (2018) GalT-KO pig lungs are highly susceptible to acute vascular rejection in baboons, which may be mitigated by transgenic expression of hCD47 on porcine blood vessels. Xenotransplantation 25:e12391

    Article  Google Scholar 

  33. Nguyen BN, Azimzadeh AM, Schroeder C et al (2011) Absence of gal epitope prolongs survival of swine lungs in an ex vivo model of hyperacute rejection. Xenotransplantation 18:94–107

    Article  Google Scholar 

  34. Azimzadeh AM, Dawson H, Nguyen BN et al (2005) aGal antigen modulates the expression of pro-inflammatory genes in hyperacute lung rejection. In: 8th International Xenotransplantation Congress, Goteborg, Sweden, September 2005

    Google Scholar 

  35. Knosalla C, Yazawa K, Behdad A et al (2009) Renal and cardiac endothelial heterogeneity impact acute vascular rejection in pig-to-baboon xenotransplantation. Am J Transplant 9:1006–1016

    Article  CAS  Google Scholar 

  36. Kim HK, Kim JE, Wi HC et al (2008) Aurintricarboxylic acid inhibits endothelial activation, complement activation, and von Willebrand factor secretion in vitro and attenuates hyperacute rejection in an ex vivo model of pig-to-human pulmonary xenotransplantation. Xenotransplantation 15:246–256

    Article  Google Scholar 

  37. Schroeder C, Allan J, Nguyen BN et al (2004) Xenogenic ex vivo perfusion of lungs from galt K/O pigs: initial results. Transplantation 78(Suppl 2):20

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Center for Transplantation Sciences and Division of Cardiac Surgery, Department of Surgery, Massachusetts General Hospital, Charlestown, MA, USA

    Lars Burdorf, Agnes M. Azimzadeh & Richard N. Pierson III

Authors
  1. Lars Burdorf
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Agnes M. Azimzadeh
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Richard N. Pierson III
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Lars Burdorf .

Editor information

Editors and Affiliations

  1. Institut d’Investigació Biomèdica de Bellvitge (IDIBELL), Hospital Duran i Reynals, L’Hospitalet de LLobregat, Barcelona, Spain

    Cristina Costa

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

Burdorf, L., Azimzadeh, A.M., Pierson, R.N. (2020). Xenogeneic Lung Transplantation Models. 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_12

Download citation

  • DOI: https://doi.org/10.1007/978-1-0716-0255-3_12

  • 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

Search

Navigation