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Recent progress and remaining hurdles toward clinical xenotransplantation.
Xenotransplantation. 2021 05; 28(3):e12681.X

Abstract

BACKGROUND

Xenotransplantation has made tremendous progress over the last decade.

METHODS

We discuss kidney and heart xenotransplantation, which are nearing initial clinical trials.

RESULTS

Life sustaining genetically modified kidney xenografts can now last for approximately 500 days and orthotopic heart xenografts for 200 days in non-human primates. Anti-swine specific antibody screening, preemptive desensitization protocols, complement inhibition and targeted immunosuppression are currently being adapted to xenotransplantation with the hope to achieve better control of antibody-mediated rejection (AMR) and improve xenograft longevity. These newest advances could probably facilitate future clinical trials, a significant step for the medical community, given that dialysis remains difficult for many patients and can have prohibitive costs. Performing a successful pig-to-human clinical kidney xenograft, that could last for more than a year after transplant, seems feasible but it still has significant potential hurdles to overcome. The risk/benefit balance is progressively reaching an acceptable equilibrium for future human recipients, e.g. those with a life expectancy inferior to two years. The ultimate question at this stage would be to determine if a "proof of concept" in humans is desirable, or whether further experimental/pre-clinical advances are still needed to demonstrate longer xenograft survival in non-human primates.

CONCLUSION

In this review, we discuss the most recent advances in kidney and heart xenotransplantation, with a focus on the prevention and treatment of AMR and on the recipient's selection, two aspects that will likely be the major points of discussion in the first pig organ xenotransplantation clinical trials.

Links

Publisher Full Text (DOI)

Authors+Show Affiliations

Meier RPH
Department of Surgery, University of Maryland School of Medicine, Baltimore, MD, USA.
Longchamp A
Department of Vascular Surgery, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne, Switzerland.
Mohiuddin M
Department of Surgery, University of Maryland School of Medicine, Baltimore, MD, USA.
Manuel O
Transplantation Center, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne, Switzerland.
Vrakas G
Department of Surgery, University of Maryland School of Medicine, Baltimore, MD, USA.
Maluf DG
Department of Surgery, University of Maryland School of Medicine, Baltimore, MD, USA.
Buhler LH
Faculty of Science and Medicine, Section of Medicine, University of Fribourg, Fribourg, Switzerland.
Muller YD
Division of Immunology and Allergy, University Hospital of Lausanne, Lausanne, Switzerland.
Pascual M
Transplantation Center, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne, Switzerland.

MeSH

AnimalsAnimals, Genetically ModifiedGraft RejectionHeterograftsHumansImmunosuppression TherapyKidney TransplantationSwineTransplantation, Heterologous

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

33759229

Citation

Meier, Raphael P H., et al. "Recent Progress and Remaining Hurdles Toward Clinical Xenotransplantation." Xenotransplantation, vol. 28, no. 3, 2021, pp. e12681.
Meier RPH, Longchamp A, Mohiuddin M, et al. Recent progress and remaining hurdles toward clinical xenotransplantation. Xenotransplantation. 2021;28(3):e12681.
Meier, R. P. H., Longchamp, A., Mohiuddin, M., Manuel, O., Vrakas, G., Maluf, D. G., Buhler, L. H., Muller, Y. D., & Pascual, M. (2021). Recent progress and remaining hurdles toward clinical xenotransplantation. Xenotransplantation, 28(3), e12681. https://doi.org/10.1111/xen.12681
Meier RPH, et al. Recent Progress and Remaining Hurdles Toward Clinical Xenotransplantation. Xenotransplantation. 2021;28(3):e12681. PubMed PMID: 33759229.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Recent progress and remaining hurdles toward clinical xenotransplantation. AU - Meier,Raphael P H, AU - Longchamp,Alban, AU - Mohiuddin,Muhammad, AU - Manuel,Oriol, AU - Vrakas,Georgios, AU - Maluf,Daniel G, AU - Buhler,Leo H, AU - Muller,Yannick D, AU - Pascual,Manuel, Y1 - 2021/03/23/ PY - 2021/02/12/revised PY - 2020/10/27/received PY - 2021/02/21/accepted PY - 2021/3/25/pubmed PY - 2021/9/18/medline PY - 2021/3/24/entrez KW - antibody KW - antibody-mediated rejection KW - antigen KW - clinical trial KW - complement KW - donor selection KW - genetic engineering KW - heart KW - kidney KW - pig KW - xenotransplantation SP - e12681 EP - e12681 JF - Xenotransplantation JO - Xenotransplantation VL - 28 IS - 3 N2 - BACKGROUND: Xenotransplantation has made tremendous progress over the last decade. METHODS: We discuss kidney and heart xenotransplantation, which are nearing initial clinical trials. RESULTS: Life sustaining genetically modified kidney xenografts can now last for approximately 500 days and orthotopic heart xenografts for 200 days in non-human primates. Anti-swine specific antibody screening, preemptive desensitization protocols, complement inhibition and targeted immunosuppression are currently being adapted to xenotransplantation with the hope to achieve better control of antibody-mediated rejection (AMR) and improve xenograft longevity. These newest advances could probably facilitate future clinical trials, a significant step for the medical community, given that dialysis remains difficult for many patients and can have prohibitive costs. Performing a successful pig-to-human clinical kidney xenograft, that could last for more than a year after transplant, seems feasible but it still has significant potential hurdles to overcome. The risk/benefit balance is progressively reaching an acceptable equilibrium for future human recipients, e.g. those with a life expectancy inferior to two years. The ultimate question at this stage would be to determine if a "proof of concept" in humans is desirable, or whether further experimental/pre-clinical advances are still needed to demonstrate longer xenograft survival in non-human primates. CONCLUSION: In this review, we discuss the most recent advances in kidney and heart xenotransplantation, with a focus on the prevention and treatment of AMR and on the recipient's selection, two aspects that will likely be the major points of discussion in the first pig organ xenotransplantation clinical trials. SN - 1399-3089 UR - https://www.unboundmedicine.com/medline/citation/33759229/Recent_progress_and_remaining_hurdles_toward_clinical_xenotransplantation_ DB - PRIME DP - Unbound Medicine ER -