» Articles » PMID: 38566098

Complement Networks in Gene-edited Pig Xenotransplantation: Enhancing Transplant Success and Addressing Organ Shortage

Overview
Journal J Transl Med
Publisher Biomed Central
Date 2024 Apr 2
PMID 38566098
Authors
Affiliations
Soon will be listed here.
Abstract

The shortage of organs for transplantation emphasizes the urgent need for alternative solutions. Xenotransplantation has emerged as a promising option due to the greater availability of donor organs. However, significant hurdles such as hyperacute rejection and organ ischemia-reperfusion injury pose major challenges, largely orchestrated by the complement system, and activated immune responses. The complement system, a pivotal component of innate immunity, acts as a natural barrier for xenotransplantation. To address the challenges of immune rejection, gene-edited pigs have become a focal point, aiming to shield donor organs from human immune responses and enhance the overall success of xenotransplantation. This comprehensive review aims to illuminate strategies for regulating complement networks to optimize the efficacy of gene-edited pig xenotransplantation. We begin by exploring the impact of the complement system on the effectiveness of xenotransplantation. Subsequently, we delve into the evaluation of key complement regulators specific to gene-edited pigs. To further understand the status of xenotransplantation, we discuss preclinical studies that utilize gene-edited pigs as a viable source of organs. These investigations provide valuable insights into the feasibility and potential success of xenotransplantation, offering a bridge between scientific advancements and clinical application.

Citing Articles

Systematic Review and Comparative Outcomes Analysis of NHP Liver Allotransplants and Xenotransplants.

Shirini K, Meier R Xenotransplantation. 2025; 32(1):e70017.

PMID: 39960351 PMC: 11832012. DOI: 10.1111/xen.70017.


Surveillance and prevention of infection in clinical xenotransplantation.

Stewart A, Fishman J Clin Microbiol Rev. 2025; 38(1):e0015023.

PMID: 39887237 PMC: 11905366. DOI: 10.1128/cmr.00150-23.

References
1.
Baldan N, Rigotti P, Calabrese F, Cadrobbi R, Dedja A, Iacopetti I . Ureteral stenosis in HDAF pig-to-primate renal xenotransplantation: a phenomenon related to immunological events?. Am J Transplant. 2004; 4(4):475-81. DOI: 10.1111/j.1600-6143.2004.00407.x. View

2.
Montgomery R, Stern J, Lonze B, Tatapudi V, Mangiola M, Wu M . Results of Two Cases of Pig-to-Human Kidney Xenotransplantation. N Engl J Med. 2022; 386(20):1889-1898. DOI: 10.1056/NEJMoa2120238. View

3.
Zhou H, Hara H, Cooper D . The complex functioning of the complement system in xenotransplantation. Xenotransplantation. 2019; 26(4):e12517. PMC: 6717021. DOI: 10.1111/xen.12517. View

4.
Asakawa R, Komatsuzawa H, Kawai T, Yamada S, Goncalves R, Izumi S . Outer membrane protein 100, a versatile virulence factor of Actinobacillus actinomycetemcomitans. Mol Microbiol. 2003; 50(4):1125-39. DOI: 10.1046/j.1365-2958.2003.03748.x. View

5.
Higginbotham L, Mathews D, Breeden C, Song M, Farris 3rd A, Larsen C . Pre-transplant antibody screening and anti-CD154 costimulation blockade promote long-term xenograft survival in a pig-to-primate kidney transplant model. Xenotransplantation. 2015; 22(3):221-30. PMC: 4930152. DOI: 10.1111/xen.12166. View