Year: 2025
Type: article
Abstract: Introduction: Xenotransplantation offers a potential solution to the critical shortage of donor organs; however, graft survival is limited by xeno-immune activation and coagulation dysregulation. Regulatory macrophages (Mregs) are known for their immunomodulatory capacity, yet their cross-species function in the context of xenotransplantation remains unclear. This study investigates the immunoregulatory properties of pig-derived Mregs (pMregs) as a potential donor-derived cellular therapy. Methods: xenogeneic inflammation model was established by exposing human M1 macrophages to pig endothelial cells to assess inflammatory cytokine responses and expression of coagulation-related genes. Results: pMregs exhibited a canonical Mreg phenotype (CD14⁺CD16⁺CD163⁺PD-L1⁺DHRS9⁺CD32⁻CD169⁻) and secreted IL-10 and TGF-β. Functionally, pMregs suppressed T-cell proliferation across pig, monkey, and human species and induced FOXP3⁺ regulatory T cells. In the xenogeneic inflammation model, pMregs attenuated inflammatory cytokine production in human M1 macrophages and downregulated mRNA expression of coagulation-associated genes, including TF and PAR-1. Discussion: These findings highlight the cross-species immunosuppressive activity and coagulation-regulatory capacity, suggesting the potential relevance to xenograft injury. pMregs may therefore serve as a promising candidate for further investigations as a donor-derived immunoregulatory cell type to complement genetically engineered pig grafts.
Source: Frontiers in Immunology
Authors: Phu Chi Vu, Nhat Minh Dang, Vinh Phuoc Nguyen, Jonghyeok Jung, Joohyun Shim, Jeong Ho Hwang, Thi Xoan Hoang, Ik Jin Yun, Jae Young Kim
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,801
Award: G8543952245
OpenAlex ID: W4417018165