Large Animal Models of Vascularized Composite Allotransplantation: A Review of Immune Strategies to Improve Allograft Outcomes

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2021 Jul 19

PMID 34276656

Citations 9

Authors

Abraham J Matar

Rebecca L Crepeau

Gerhard S Mundinger

Curtis L Cetrulo Jr

Radbeh Torabi

Affiliations

Soon will be listed here.

Abstract

Over the past twenty years, significant technical strides have been made in the area of vascularized composite tissue allotransplantation (VCA). As in solid organ transplantation, the allogeneic immune response remains a significant barrier to long-term VCA survival and function. Strategies to overcome acute and chronic rejection, minimize immunosuppression and prolong VCA survival have important clinical implications. Historically, large animals have provided a valuable model for testing the clinical translatability of immune modulating approaches in transplantation, including tolerance induction, co-stimulation blockade, cellular therapies, and perfusion. Recently, significant advancements have been made in these arenas utilizing large animal VCA models. In this comprehensive review, we highlight recent immune strategies undertaken to improve VCA outcomes with a focus on relevant preclinical large animal models.

Citing Articles

An innovative ear transplantation for vascularized composite allotransplantation research in porcine model.

Holguin-Ruiz J, Rodriguez L, Ferreira-Galvao F, Munoz-Botina J, Bedoya Duque M, Varela-Vasquez M Sci Rep. 2024; 14(1):30896.

PMID: 39730666 PMC: 11680874. DOI: 10.1038/s41598-024-81908-8.

Autologous porcine VRAM flap model for VCA research.

Blades C, Dumanian Z, Wang Y, Wang Z, Li B, Washington K Front Transplant. 2024; 3:1504959.

PMID: 39712036 PMC: 11659244. DOI: 10.3389/frtra.2024.1504959.

Transcriptome profiling of immune rejection mechanisms in a porcine vascularized composite allotransplantation model.

Zhang L, Arenas Hoyos I, Helmer A, Banz Y, Zubler C, Lese I Front Immunol. 2024; 15:1390163.

PMID: 38840906 PMC: 11151749. DOI: 10.3389/fimmu.2024.1390163.

Machine Perfusion Enables 24-h Preservation of Vascularized Composite Allografts in a Swine Model of Allotransplantation.

Goutard M, Tawa P, Berkane Y, Andrews A, Pendexter C, de Vries R Transpl Int. 2024; 37:12338.

PMID: 38813393 PMC: 11133529. DOI: 10.3389/ti.2024.12338.

Successful Extension of Vascularized Composite Allograft Perfusion Cold Storage to 24 h in a Rat Hindlimb Transplant Model.

Ng P, Yoeli D, Huang J, Luo Y, Wang Y, Li B Transplant Direct. 2024; 10(6):e1623.

PMID: 38757052 PMC: 11098188. DOI: 10.1097/TXD.0000000000001623.

References

Kueckelhaus M, Fischer S, Seyda M, Bueno E, Aycart M, Alhefzi M . Vascularized composite allotransplantation: current standards and novel approaches to prevent acute rejection and chronic allograft deterioration. Transpl Int. 2015; 29(6):655-62. PMC: 4785085. DOI: 10.1111/tri.12652. View

Pomahac B, Pribaz J, Eriksson E, Bueno E, Diaz-Siso J, Rybicki F . Three patients with full facial transplantation. N Engl J Med. 2011; 366(8):715-22. DOI: 10.1056/NEJMoa1111432. View

Hettiaratchy S, Melendy E, Randolph M, Coburn R, Neville Jr D, Sachs D . Tolerance to composite tissue allografts across a major histocompatibility barrier in miniature swine. Transplantation. 2004; 77(4):514-21. DOI: 10.1097/01.tp.0000113806.52063.42. View

Cetrulo Jr C, Li K, Salinas H, Treiser M, Schol I, Barrisford G . Penis Transplantation: First US Experience. Ann Surg. 2017; 267(5):983-988. DOI: 10.1097/SLA.0000000000002241. View

Giannoukakis N, Phillips B, Finegold D, Harnaha J, Trucco M . Phase I (safety) study of autologous tolerogenic dendritic cells in type 1 diabetic patients. Diabetes Care. 2011; 34(9):2026-32. PMC: 3161299. DOI: 10.2337/dc11-0472. View

Wang Y, Anggelia M, Chuang W, Cheng H, Mao Q, Zelken J . Combined Anti-CD154/CTLA4Ig Costimulation Blockade-Based Therapy Induces Donor-Specific Tolerance to Vascularized Osteomyocutaneous Allografts. Am J Transplant. 2016; 16(7):2030-41. DOI: 10.1111/ajt.13694. View

Silverman R, Banks N, DeTolla L, Shipley S, Panda A, Sanchez R . A heterotopic primate model for facial composite tissue transplantation. Ann Plast Surg. 2008; 60(2):209-16. DOI: 10.1097/SAP.0b013e318061b792. View

Kawai T, Cosimi A, Wee S, Houser S, Andrews D, Sogawa H . Effect of mixed hematopoietic chimerism on cardiac allograft survival in cynomolgus monkeys. Transplantation. 2002; 73(11):1757-64. DOI: 10.1097/00007890-200206150-00011. View

Kaufman C, Ouseph R, Marvin M, Manon-Matos Y, Blair B, Kutz J . Monitoring and long-term outcomes in vascularized composite allotransplantation. Curr Opin Organ Transplant. 2013; 18(6):652-8. DOI: 10.1097/MOT.0000000000000025. View

10.

Mundinger G, Nam A, Hui-Chou H, Stanwix M, Jones L, Drachenberg C . Nonhuman primate model of fibula vascularized composite tissue allotransplantation demonstrates donor-recipient bony union. Plast Reconstr Surg. 2011; 128(6):1193-1204. DOI: 10.1097/PRS.0b013e318230c5d0. View

11.

Villamaria C, Fries C, Spencer J, Roth M, Davis M . Hydrogen sulfide mitigates reperfusion injury in a porcine model of vascularized composite autotransplantation. Ann Plast Surg. 2013; 72(5):594-8. DOI: 10.1097/SAP.0000000000000021. View

12.

Leonard D, Kurtz J, Mallard C, Albritton A, Duran-Struuck R, Farkash E . Vascularized composite allograft tolerance across MHC barriers in a large animal model. Am J Transplant. 2014; 14(2):343-55. PMC: 3971524. DOI: 10.1111/ajt.12560. View

13.

Schnider J, Weinstock M, Plock J, Solari M, Venkataramanan R, Zheng X . Site-specific immunosuppression in vascularized composite allotransplantation: prospects and potential. Clin Dev Immunol. 2013; 2013:495212. PMC: 3586464. DOI: 10.1155/2013/495212. View

14.

Morelli A, Thomson A . Orchestration of transplantation tolerance by regulatory dendritic cell therapy or in-situ targeting of dendritic cells. Curr Opin Organ Transplant. 2014; 19(4):348-56. PMC: 4204930. DOI: 10.1097/MOT.0000000000000097. View

15.

Ge W, Jiang J, Arp J, Liu W, Garcia B, Wang H . Regulatory T-cell generation and kidney allograft tolerance induced by mesenchymal stem cells associated with indoleamine 2,3-dioxygenase expression. Transplantation. 2010; 90(12):1312-20. DOI: 10.1097/TP.0b013e3181fed001. View

16.

Krishnan G, Du C, Fishman J, Foreman A, Lott D, Farwell G . The current status of human laryngeal transplantation in 2017: A state of the field review. Laryngoscope. 2017; 127(8):1861-1868. DOI: 10.1002/lary.26503. View

17.

Morelon E, Petruzzo P, Kanitakis J . Chronic rejection in vascularized composite allotransplantation. Curr Opin Organ Transplant. 2018; 23(5):582-591. DOI: 10.1097/MOT.0000000000000571. View

18.

Tonsho M, Lee S, Aoyama A, Boskovic S, Nadazdin O, Capetta K . Tolerance of Lung Allografts Achieved in Nonhuman Primates via Mixed Hematopoietic Chimerism. Am J Transplant. 2015; 15(8):2231-9. PMC: 4569127. DOI: 10.1111/ajt.13274. View

19.

Gajanayake T, Olariu R, Leclere F, Dhayani A, Yang Z, Bongoni A . A single localized dose of enzyme-responsive hydrogel improves long-term survival of a vascularized composite allograft. Sci Transl Med. 2014; 6(249):249ra110. DOI: 10.1126/scitranslmed.3008778. View

20.

Oh B, Furtmuller G, Fryer M, Guo Y, Messner F, Krapf J . Vascularized composite allotransplantation combined with costimulation blockade induces mixed chimerism and reveals intrinsic tolerogenic potential. JCI Insight. 2020; 5(7). PMC: 7205254. DOI: 10.1172/jci.insight.128560. View