a-preclinical-model-orthotopic-heart-transplantation-bama-miniature

A Preclinical Model of Orthotopic Heart Transplantation in Bama Miniature Pigs Using Biatrial Technique

Although significant progress has been made in heart transplantation, issues such as graft preservation, primary graft dysfunction, cardiac allograft ...

a-mouse-model-donor-heart-lymphatic-ablation-via-electrocautery-for

A Mouse Model of Donor Heart Lymphatic Ablation <em>via</em> Electrocautery for Transplantation Research

Although cardiac lymphatic vessels have garnered increasing attention in recent years, the relationship between the donor cardiac lymphatic system and ...

implantation-left-ventricular-assist-device-lvad-juvenile-landrace

Implantation of Left Ventricular Assist Device (LVAD) in Juvenile Landrace Swine: A LVAD Implantation Model of Pediatric Heart Failure

A pediatric left ventricular assist device (LVAD) implantation model was established to simulate pediatric LVAD support and research the mechanism of ...

a-surgical-method-for-subvalvular-structure-intervention-through

A Surgical Method for Subvalvular Structure Intervention Through a Transaortic Approach in Normal Bama Pigs

Subvalvular structure abnormalities leading to left ventricular outflow tract (LVOT) alterations and myocardial hypertrophy are characteristic anatomical ...

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

Organ transplantation is the preferred treatment option for end-stage organ failure. Although immunosuppressants are effective for preventing the occurrence of acute rejection, they also cause a series of side effects in transplant recipients. To improve the quality of patient survival, a new therapeutic strategy that has fewer side effects than current immunosuppressive regimens and can induce allograft immune tolerance and effectively prevent transplant rejection is needed. In this context, regulatory T cells (Tregs) are considered to be promising research targets. With the increasing understanding of the immunomodulatory role of Tregs, the use of Treg-based cellular therapies has shifted from prevention/treatment of autoimmune diseases to clinical trials for organ transplantation. This review describes the phenotype and in vitro expansion of Tregs and the mechanisms by which they exert immunomodulatory effects in transplantation immunity, highlights recent clinical trial data on Treg-based cellular therapies in transplantation, and describes future directions and limitations.

Regulatory T cells induce transplant immune tolerance.

Regulatory T cells (Tregs) are indispensable for the maintenance of immune tolerance. The purpose of this study was to investigate the effect of the interaction of the lncRNA PVT1 and miR-146a on Treg autophagy and reveal the mechanism to alleviate transplant rejection. PVT1 and miR-146a expression levels were analyzed by qRT-PCR. Bioinformatic analysis and methylation profiling were used to determine the relationship between PVT1 and miR-146a. Altered autophagic status in Tregs was detected by western blotting. The effect of autophagy on Treg function was assessed in cell coculture in vitro and in animal models. Our results showed that PVT1 expression was reduced in Tregs during rejection and negatively correlated with miR-146a expression. Higher PVT1 expression was associated with higher autophagy in Tregs. Further, highly autophagic Tregs had stronger inhibitory effects on CD4 T cells in vitro, prolonged allograft survival and alleviated rejection in vivo. Mechanistic studies showed that overexpression of PVT1 enhanced TNF receptor-associated factor (TRAF) 6 expression by directly targeting miR-146a. MiR-146a overexpression reversed PVT1-induced Treg autophagy and inhibited PVT1-induced TRAF6 expression. The present study shows a novel regulatory pathway of the autophagy program that comprises PVT1, miR-146a, and TRAF6. Our findings may provide potential targets and new therapeutic strategies for transplant rejection.

The lncRNA PVT1 regulates autophagy in regulatory T cells to suppress heart transplant rejection in mice by targeting miR-146a.

Cardiovascular disease is the most common cause of death worldwide, resulting in millions of deaths annually. Currently, there are still some deficiencies in the treatment of cardiovascular diseases. Innovative surgical treatments are currently being developed and tested in response to this situation. Large animal models, which are similar to humans in terms of anatomy, physiology, and genetics, play a crucial role in connecting basic research and clinical applications. This article reviews recent preclinical studies and the latest clinical advancements in cardiovascular disease based on large animal models, with a focus on targeted delivery, neural regulation, cardiac remodeling, and hemodynamic regulation. It provides new perspectives and ideas for clinical translation and offers new methods for clinical treatment.

Advances in preclinical surgical therapy of cardiovascular diseases.

Xenotransplantation offers a transformative solution to the global organ shortage crisis. However, the survival of xenografts remains limited despite various proposed strategies. In this study, we present an endothelial cell protection strategy that extends graft survival through the  construction of biomimetic glycan-enriched nanofibers. These biomimetic glycan-enriched molecules specifically target integrin αβ and form a polysaccharide-structured nanofiber network on the vascular endothelial surface. This network protects endothelial cells without compromising their normal physiological functions. The constructed biomimetic glycan-enriched layer significantly increased the xenograft survival by 1.64-fold compared to the untreated groups. This work introduces a novel strategy to enhance the survival of heart xenografts.

In Situ Biomimetic Glycocalyx Layer Protects Endothelial Damage in Xenotransplantation.

Arrhythmogenic cardiomyopathy (ACM) confers elevated risk of ventricular arrhythmias and sudden cardiac death, yet limitations in early lesion sampling and model development continue to hinder mechanistic and translational research. Clinical, pathological, and mutational profiles were examined in 24 individuals with ACM harboring  variants. Among these, a patient carrying the c.1132C>T mutation exhibited the earliest onset and presented both structural cardiac abnormalities and major adverse cardiovascular events. To facilitate disease modeling, the c.1147C>T variant-a previously reported pathogenic substitution located proximal to position c.1132 in -was selected to enhance the feasibility of generating a porcine model. The BE3 gene editing system was used to induce C>T mutation. Two single guide RNAs targeting the  gene were designed (sgRNA1 for c.1132C>T and sgRNA2 for c.1147C>T), yielding editing efficiencies of 42.9% and 25.9%, respectively. SgRNA1 was used to generate   porcine fetal fibroblasts. A total of 14 cloned piglets were produced, including 11 viable and three stillborn   individuals. By 24 months of age,   pigs developed premature ventricular contractions and right ventricular dilatation. Histological analysis revealed adipocyte infiltration within the right ventricular wall, and electron microscopy demonstrated reduced desmosomal length and electron density consistent with desmosomal dysfunction. Transcriptomic profiling showed high expression of genes associated with lipid catabolic processes. This study established the first   porcine model of ACM using BE3-mediated base editing, providing a valuable platform for elucidating early pathogenic mechanisms and evaluating therapeutic interventions.

Generation of a  heterozygous knockout pig model of arrhythmogenic cardiomyopathy.

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.

Inhibition of T cell polyamine metabolism promotes transplant acceptance by modulating cytotoxic CD8 T cell differentiation.

Hypertension-associated aortic dissection (HTN-AD) features intense immune activation and extracellular matrix disruption, yet the cellular programs that promote aortic-wall stabilization remain unclear. We aimed to identify macrophage states associated with vascular integrity and to determine whether these states could be mechanistically or therapeutically leveraged.

ArticleTotal : 5	Year
Publication title	2025
Publication title	2026
Publication title	2026
Publication title	2026
Publication title	2026

Article	Year
Regulatory T cells induce transplant immune tolerance. Transplant immunology\| PubMed ID: 34020045	2021
The lncRNA PVT1 regulates autophagy in regulatory T cells to suppress heart transplant rejection in mice by targeting miR-146a. Cellular immunology\| PubMed ID: 34214903	2021
Advances in preclinical surgical therapy of cardiovascular diseases. International journal of surgery (London, England)\| PubMed ID: 38701509	2024
In Situ Biomimetic Glycocalyx Layer Protects Endothelial Damage in Xenotransplantation. Nano letters\| PubMed ID: 40062533	2025
Generation of a heterozygous knockout pig model of arrhythmogenic cardiomyopathy. Zoological research\| PubMed ID: 41603024	2026
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
SPP1 fibrogenic macrophages mediate protective fibrotic remodeling and promote vascular stability in hypertension-associated aortic dissection. BMC medicine\| PubMed ID: 41840626	2026

Peiyuan Li

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