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What Genetic Modifications of Source Pigs Are Essential and Sufficient for Cell, Tissue, and Organ Xenotransplantation?
Transpl Int
December 2024
Molecular Animal Breeding and Biotechnology, Gene Center and Department of Veterinary Sciences, LMU Munich, Munich, Germany.
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.
View Article and Find Full Text PDFGeneration and characterization of genetically modified pigs with GGTA1/β4GalNT2/CMAH knockout and human CD55/CD47 expression for xenotransfusion studies.
Sci Rep
December 2024
Jiangsu Key Laboratory of Xenotransplantation, Nanjing Medical University, Nanjing, 211166, China.
Pig red blood cells (pRBCs) represent a promising alternative to address the shortage in transfusion medicine. Nonetheless, a major obstacle to their clinical implementation is immunological rejection. In this study, we generated transgenic pigs expressing human CD47 (hCD47) and CD55 (hCD55) in α1,3-galactosyltransferase KO/β-1,4-N-acetyl-galactosaminyl transferase 2 KO/cytidine monophosphate-N-acetylneuraminic acid hydroxylase KO (TKO) pigs using CRISPR/Cas9 technology.
View Article and Find Full Text PDFSubstitution of Glutamic Acid at Position 71 of DRβ1*04:01 and Collagen-Specific Tolerance Without Alloreactivity.
Arthritis Rheumatol
November 2024
University of Colorado, Anschutz Medical Campus, Aurora, Colorado.
Objective: The DRB1 locus is strongly associated with both susceptibility and resistance to rheumatoid arthritis (RA). DRB1 alleles encoding the VKA or VRA epitope in positions 11, 71, and 74 confer the highest risk of developing RA, whereas the allele encoding VEA is protective. We therefore investigated the feasibility of creating antigen-specific tolerance without inducing alloreactivity by replacing lysine with glutamic acid at position 71 in DRβ1*04:01.
View Article and Find Full Text PDFComplement and complement regulatory protein in allogeneic and xenogeneic kidney transplantation.
Transplant Rev (Orlando)
January 2025
Department of Urology, Osaka University Graduate School of Medicine, Japan.
Kidney transplantation is the most optimal treatment for patients with end-stage renal disease, offering significant improvements in patient outcomes over dialysis. However, the potential for immune rejection, where the recipient's immune system attacks the transplanted kidney, can compromise transplant success. The complement system, a key component of the immune response, plays a crucial role in both acute and chronic rejection, including T-cell- and antibody-mediated rejection.
View Article and Find Full Text PDFTertiary Lymphoid Structures and Immunotherapy: Challenges and Opportunities.
Methods Mol Biol
November 2024
Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, CT, USA.
Tertiary lymphoid structures (TLS) are accumulations of lymphoid cells that arise in ectopic sites through the process of lymphoid neogenesis in chronic inflammation in autoimmunity, microbial infections, organ rejection, aging, and cancer. Their cellular composition and function and regulation via members of the lymphotoxin (LT)/tumor necrosis factor (TNF) family resemble that of secondary lymphoid organs (SLOs). Tumor-associated (TA)-TLS can be associated with favorable clinical outcomes.
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