Korean J Transplant.  2022 Nov;36(Supple 1):S334. 10.4285/ATW2022.F-4778.

Generation and characterization of regulatory macrophages for xenotransplantation

• Hoang TX
• Kim JY
• Pham HL
• Nguyen NL
• Jeong J
• Kim YJ
• Tran TM
• Kim MH
• Lee MK

• KMID: 2535561
• DOI: http://doi.org/10.4285/ATW2022.F-4778

Abstract

The outstanding role of regulatory macrophages (Mregs) in promoting immunomodulation allowed the clinical application of Mregs-based therapies for controlling unwanted immune responses, especially in the field of transplantation. The major obstacle known to prevent pig-to-human xenotransplantation is the interaction between the human natural anti-Gal antibody and the -Gal epitope (Gal1-3Gal1-4GlcNAc-R). A promising strategy to eliminate the interaction between human immune cells and porcine transplanted organs is to generate Mregs, which is tolerant to -Gal epitope. We established a protocol to generate and character-ize Mregs from human monocytes THP-1 cells, specifically resistant to porcine antigen -Gal. The cells were stimulated with a se-ries of stimulants including GM-CSF, IFN-, dexamethasone, vitamin D3, and porcine-specific antigen -Gal. The generated Mregs displayed fiber-like morphology and high levels of CD16, CD163, CD206, Mer-TK, DHRS9, increased mitochondrial fusion and in-duced histone H3 lysine 4 monomethylation (H2K27me1). Importantly, Mregs showed suppressed inflammatory mediators gene expression and decreased tissue factor-coagulation signaling under co-culture with pig endothelial cells. Our results illustrate a feasible approach for generating functional Mregs which would be an effective and safe tool for pig-to-human xenotransplantation.