What Genetic Modifications of Source Pigs Are Essential and Sufficient for Cell, Tissue, and Organ Xenotransplantation?

Autor:	Ali A; Molecular Animal Breeding and Biotechnology, Gene Center and Department of Veterinary Sciences, LMU Munich, Munich, Germany.; Center for Innovative Medical Models (CiMM), LMU Munich, Oberschleißheim, Germany., Kurome M; Molecular Animal Breeding and Biotechnology, Gene Center and Department of Veterinary Sciences, LMU Munich, Munich, Germany.; Center for Innovative Medical Models (CiMM), LMU Munich, Oberschleißheim, Germany., Kessler B; Molecular Animal Breeding and Biotechnology, Gene Center and Department of Veterinary Sciences, LMU Munich, Munich, Germany.; Center for Innovative Medical Models (CiMM), LMU Munich, Oberschleißheim, Germany., Kemter E; Molecular Animal Breeding and Biotechnology, Gene Center and Department of Veterinary Sciences, LMU Munich, Munich, Germany.; Center for Innovative Medical Models (CiMM), LMU Munich, Oberschleißheim, Germany.; Interfaculty Center for Endocrine and Cardiovascular Disease Network Modelling and Clinical Transfer (ICONLMU), LMU Munich, Munich, Germany.; German Center for Diabetes Research (DZD), Neuherberg, Germany., Wolf E; Molecular Animal Breeding and Biotechnology, Gene Center and Department of Veterinary Sciences, LMU Munich, Munich, Germany.; Center for Innovative Medical Models (CiMM), LMU Munich, Oberschleißheim, Germany.; Interfaculty Center for Endocrine and Cardiovascular Disease Network Modelling and Clinical Transfer (ICONLMU), LMU Munich, Munich, Germany.; German Center for Diabetes Research (DZD), Neuherberg, Germany.
Jazyk:	angličtina
Zdroj:	Transplant international : official journal of the European Society for Organ Transplantation [Transpl Int] 2024 Dec 04; Vol. 37, pp. 13681. Date of Electronic Publication: 2024 Dec 04 (Print Publication: 2024).
DOI:	10.3389/ti.2024.13681
Abstrakt:	Xenotransplantation of porcine organs has made remarkable progress towards clinical application. A key factor has been the generation of genetically multi-modified source pigs for xenotransplants, protected against immune rejection and coagulation dysregulation. While efficient gene editing tools and multi-cistronic expression cassettes facilitate sophisticated and complex genetic modifications with multiple gene knockouts and protective transgenes, an increasing number of independently segregating genetic units complicates the breeding of the source pigs. Therefore, an optimal combination of essential genetic modifications may be preferable to extensive editing of the source pigs. Here, we discuss the prioritization of genetic modifications to achieve long-term survival and function of xenotransplants and summarise the genotypes that have been most successful for xenogeneic heart, kidney, and islet transplantation. Specific emphasis is given to the choice of the breed/genetic background of the source pigs. Moreover, multimodal deep phenotyping of porcine organs after xenotransplantation into human decedents will be discussed as a strategy for selecting essential genetic modifications of the source pigs. In addition to germ-line gene editing, some of these modifications may also be induced during organ preservation/perfusion, as demonstrated recently by the successful knockdown of swine leukocyte antigens in porcine lungs during ex vivo perfusion. Competing Interests: Authors EK and EW are cofounders of the company XTransplant GmbH, Starnberg. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2024 Ali, Kurome, Kessler, Kemter and Wolf.)
Databáze:	MEDLINE
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