Xenotransplantation in Healthcare: A Literature Review of Clinical Advances, Immunological Barriers, and Ethical Challenges
Article Sidebar
Main Article Content
Abstract
Background: The global shortage of donor organs remains a critical challenge in healthcare, driving the search for alternative strategies to reduce waiting list mortality. Xenotransplantation the transplantation of organs, tissues, or cells across species—has emerged as a promising solution. Advances in genetic engineering, immunological modulation, and tissue preservation have accelerated progress, yet clinical translation remains constrained by unresolved biological and ethical barriers.
Objectives: This review aimed to systematically evaluate the current evidence on xenotransplantation, focusing on its safety, efficacy, immunological challenges, and societal implications, in order to assess its readiness for integration into clinical practice.
Methods: A literature review was conducted in this study. PubMed and Scopus were searched for publications between January 2020 and August 2025. Eligible studies included clinical reports, preclinical experiments, mechanistic investigations, and survey-based studies addressing xenotransplantation. Data were extracted on study design, xenograft type, intervention details, and reported outcomes. Due to heterogeneity, results were synthesized narratively.
Results: Twenty studies were included. Clinical reports demonstrated that genetically engineered pig organs could function in humans for several weeks, though rejection, coagulation dysregulation, and viral reactivation remain obstacles. Preclinical models in nonhuman primates and rodents confirmed prolonged graft survival with multigene donor modifications and costimulation blockade. Cellular approaches, including porcine islets and ovarian tissue grafts, showed promise in metabolic and reproductive medicine. Surveys revealed moderate public support but persistent concerns regarding safety and ethics.
Conclusion: Xenotransplantation has progressed from experimental proof-of-concept to early clinical application. While advances in genetic editing, immunosuppression, and graft preservation are encouraging, clinical translation will require overcoming immunological and infectious barriers, alongside addressing societal and ethical considerations, to ensure safe and sustainable implementation in healthcare.
Article Details
This work is licensed under a Creative Commons Attribution 4.0 International License.
How to Cite
References
Mohiuddin MM, Singh AK, Corcoran PC, Thomas ML, Clark JR, Lewis BG, et al. Genetically engineered pig heart transplantation in a human: Case report. Lancet. 2023;401(10387):179–189.
Shasha L, Grischenko O, Hryhorovych M, Vasianovich Y, Glushchenko O, Sun L, et al. Slow cryopreservation improves structural and functional preservation of adrenal xenografts in rats. Cryobiology. 2021;98:175–183.
Coe TM, Markmann JF, Rickert CG. Current status of clinical islet xenotransplantation. Curr Opin Organ Transplant. 2020;25(5):465–472.
Song M, Cooper DKC, Hara H, Wang L, Milewski K, Liu H, et al. CD46 expression reduces coagulation and inflammation but not immune cell recruitment in pig-to-primate islet xenotransplantation. Xenotransplantation. 2021;28(6):e12707.
Zhang X, He J, Wang J, Chen H, Chen G. Current status of pig-to-nonhuman primate organ xenotransplantation. Sci China Life Sci. 2021;64(5):752–767.
Zidan A, Alanazi R, Naeem H, Ekser B, Ayares D, Cooper DKC. Coagulation dysregulation in pig-to-primate kidney xenotransplantation: Current understanding and future directions. Am J Hematol. 2025;100(1):55–66.
Arner A, Algharib SA, Hohn C, Reischl M, Pollmann M, Nivarthi H, et al. Zebrafish xenotransplantation models of acute lymphoblastic leukemia reveal niche interactions and disease dissemination. PLoS One. 2024;19(3):e0301817.
Maeda A, Kobayashi T. Innate immune responses in xenotransplantation: From cellular mechanisms to clinical relevance. Front Immunol. 2022;13:857304.
Cooper DKC, Ayares D, Tector AJ, Pierson RN. Sensitization and xenotransplantation: Alloantibodies versus xenoantibodies. Hum Immunol. 2023;84(5):392–400.
Padilla LA, Wainwright DA, Macedo C, Tector AJ, Mohiuddin MM, Cooper DKC, et al. Public attitudes toward xenotransplantation in the United States: Results from a national survey. Am J Transplant. 2024;24(7):893–902.
Lucander ACK, Tanabe T, Cooper DKC. Calcium and phosphate disturbances after renal xenotransplantation: Implications for clinical translation. Xenotransplantation. 2022;29(6):e12755.
Cooper DKC, Hara H, Iwase H, Yamamoto T, Li Q, Ezzelarab M, et al. Pig kidney xenotransplantation: Progress toward clinical trials. J Am Soc Nephrol. 2020;31(1):12–21.
Zehnle PMA, Kuhl AA, Radke TF, von Bonin F, Jacobs R, Koehl U, et al. Overexpression of BCL-XL enhances ex vivo expansion and in vivo engraftment of human hematopoietic stem cells. Haematologica. 2024;109(2):476–489.
Huang W, He J, Li M, Xu J, Chen H, Liu Q, et al. Prolonged cold ischemia time impairs neonatal porcine islet xenotransplantation in diabetic mice. Xenotransplantation. 2021;28(2):e12649.
Man L, Park Y, Nam K, Velthut-Meikas A, Kim H, Dahan M, et al. IGF-1 delivery enhances human ovarian tissue xenotransplantation outcomes in mice. Fertil Steril. 2021;115(5):1295–1305.
Li Q, Ren B, Chen H, Zhao X, Xu J, Zhou L, et al. Tissue-engineered chambers improve vascularization and survival of islet xenografts in mice. PLoS One. 2020;15(8):e0237078.
Ñaupas LVS, Amorim CA, Lucci CM, Carvalho AA. α-Lipoic acid supplementation improves follicular survival and development after ovine ovarian tissue xenografting. Reprod Fertil Dev. 2021;33(5):295–304.
Zeisig BB, Göthert JR, Enver T. A protocol for generating human acute myeloid leukemia models by xenotransplantation. STAR Protoc. 2021;2(3):100651.
Morgan A, Dust T, Abdouh M, Yao J, Alvarez P, Nita F, et al. Human adipose-derived stem cells reduce anastomotic leakage in a rat colorectal surgery model. Dis Colon Rectum. 2020;63(9):1268–1276.
Yoon CH, Kim MK, Wee WR, Kim SJ, Kim DH, Hyon JY, et al. Rituximab improves survival of GTKO pig corneal xenografts in rhesus macaques. Xenotransplantation. 2020;27(6):e12626.