a-standardized-murine-model-with-three-person-workflow-for-studying

A Standardized Murine Model with a Three-Person Workflow for Studying Acute Cellular and Antibody-Mediated Rejection in Xenotransplantation

Despite recent advancements in xenotransplantation, acute rejection remains a major barrier to its clinical application. Acute cellular rejection (ACR) ...

Chinese Academy of Medical Sciences and Peking Union Medical College

First Teaching Hospital of Tianjin University of Traditional Chinese Medicine

A novel quasi-homogeneous supercooling approach expands preservation time for donor hearts.

Cardiac allograft vasculopathy (CAV) is a major barrier to long-term survival after heart transplantation, characterized by progressive vascular remodeling and luminal narrowing. Fibrosis is one of the key pathological features of CAV progression, but its underlying mechanisms remain unclear. This study aims to investigate the mechanisms of CAV-associated vascular fibrosis and explore potential therapeutic targets.

Blocking AREG-EGFR signaling attenuates pan-arterial fibrosis in chronic cardiac allograft rejection.

Polyamines, particularly spermidine, are well-documented for their cardiovascular protective, antitumor, and longevity-promoting properties. However, their role in heart transplantation, and specifically the contribution of T-cell polyamine metabolism to transplant acceptance, remains undefined. In this study, we integrated preclinical and clinical studies to address this gap. We found that polyamine metabolism was significantly upregulated in T cells during acute rejection (AR) in both murine allografts and human AR samples. Critically, conditional inhibition of polyamine metabolism in T cells completely prevents AR and promotes long-term graft survival. Mechanistically, we found that polyamine metabolism is crucial for the differentiation of cytotoxic CD8 T cells. Further, this regulatory effect was mediated by polyamine-dependent hypusination of eukaryotic initiation factor 5A (eIF5A), with inhibition of T cell eIF5A hypusination recapitulating the anti-AR effects of polyamine blockade. Our study identifies T cell polyamine metabolism as a critical regulator of cytotoxic CD8 T cell differentiation and AR in heart transplantation. Targeting this pathway holds promise as a novel therapeutic strategy for treating AR.

Article	Year
A novel quasi-homogeneous supercooling approach expands preservation time for donor hearts. JTCVS techniques\| PubMed ID: 41658865	2026
Blocking AREG-EGFR signaling attenuates pan-arterial fibrosis in chronic cardiac allograft rejection. Theranostics\| PubMed ID: 41799192	2026
Inhibition of T cell polyamine metabolism promotes transplant acceptance by modulating cytotoxic CD8 T cell differentiation. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons\| PubMed ID: 41812731	2026

Yuqi An

Biography

JoVE Journal Publications

Other Publications