Immune Rejection Research Articles (Page 1)

Insulin-producing β cell replacement therapies show promise for treating type 1 diabetes (T1D), but challenges such as donor shortages and immune rejection persist. Stem cell-derived β cells (sBC) provide a renewable source but remain susceptible to immune attack. We engineered human pluripotent stem cells to express either the wild type (WT) or a high-affinity mutant (Mut) variant (rs1058402, G>A; Ala67Thr) of the natural killer (NK) and T cell checkpoint inhibitor CD155 before differentiation into sBC. Modified sBC maintained up-regulated CD155 expression and showed enhanced binding to co-receptor ligands. Co-culture studies revealed CD155-expressing sBC suppressed autoreactive CD8+ T cell and NK cell activation, reducing immune cell-mediated sBC destruction and cytotoxic molecule secretion by preferentially engaging the coinhibitory receptor TIGIT. This protection was lost with TIGIT blockade, affirming the role of CD155-TIGIT signaling in antagonizing immune cell cytotoxicity. Our findings suggest that high-affinity CD155 expression enhances immune evasion of sBC, improving their potential as a therapy for T1D.

Currently, the field of organ transplantation faces serious challenges such as organ supply shortages and immune rejection. As an emerging 3D printing technology, bioprinting holds promise as a potential solution to these issues. This paper aims to comprehensively analyze the core foundational elements, classification of key technologies, and application progress of bioprinting in organ regeneration. Through literature review and case studies, it explores the current status of bioprinting applications in constructing complex tissue and organ structures, identifying challenges such as bioink performance optimization, seed cell selection, and bioprinting precision. Empirical evidence demonstrates bioprinting's transformative potential for organ regeneration, but critical challenges persistparticularly in bioink biocompatibility, cell viability preservation, and structural durability of printed constructsall requiring targeted research interventions. Future research should focus on developing novel bioinks, optimizing seed cell sources, and enhancing the precision and efficiency of bioprinting to advance organ regeneration technology.

The rapid growth of generative AI (GAI) has transformed how artistic works are created and raised new challenges for copyright law. The traditional safe harbor regime is under strain. Due to widespread and instant outputs by GAI, the old notice-and-takedown approach no longer works. This paper reviews the main academic views on the liability of GAI platforms and the scope of safe harbor protection. It identifies three main positions: complete rejection of immunity, conditional immunity with new duties, and structural reform of liability rules. It explains the reasons and limits of each view. Based on this review, the paper proposes a duty-based exemption model: a limited immunity system that matches the platforms level of control, the predictability of risk, and the benefits received. This model aims to balance copyright protection with technological innovation.

Backgrounds: Heart transplantation remains the gold-standard therapy for end-stage heart failure. However, immune rejection of the transplanted heart critically compromises long-term survival rates. Accumulating evidence suggests that the contribution of Lipopolysaccharide (LPS)-induced innate immunity to immune rejection has been historically underappreciated, which may partially explain the limited efficacy of current immunosuppressive regimens in clinical practice. Methods: Using a novel mouse model that combines LPS-tolerance with heart transplantation, we systematically explore how LPS-tolerance modulates the immune microenvironment of transplanted hearts through epigenetic remodeling and metabolic reprogramming. By transferring whole bone marrow from CAG -Cre; R26-tdTomato mice to irradiated C57BL/6J mice, chimeric mice were generated. Subsequently, C57BL/6J mice received LPS-educated hematopoietic stem cells (HSCs) before undergoing heart transplantation. Results: Here, we showed that LPS exposure altered the transcriptome of HSCs and induced myelopoiesis. Preliminary findings showed LPS-educated HSCs generate epigenetically modified macrophages that provided significantly better protection against cardiac allografts rejection. An increase in CD206 + M2 macrophages were identified in LPS-treated allografts associated with the presence of the epigenetic marker H3K27ac, indicating active gene expression. Furthermore, by integrating the established heart transplantation biobank with comprehensive multi-omics analyses, such as transcriptomics and epigenomics, we aimed to identify distinct molecular signatures associated with this LPS tolerance-driven graft protection. The novel therapeutic targets for attenuating immune rejection via trained immunity were identified and their clinical translational potential being validated. Conclusions: Distinct from conventional immunosuppressive agents targeting T cell-mediated adaptive immunity, we pioneer a paradigm shift by investigating the role of LPS-induced innate immunity in cardiac allograft rejection. The clinical translation of these findings is anticipated to revolutionize immunosuppressive strategies, ultimately benefiting a substantial population of heart failure patients.

Introduction: Partial Heart Transplants (PHT) retain shortcomings intrinsic to transplantation, including the requirement to transplant grafts urgently after donation to maintain cellular viability.We evaluated the graft viability growth potential, hemodynamic function and immune rejection of pulmonary valve partial heart transplants vitrified for a month in a porcine model. Methods: PHT grafts from GFP+ donor piglets were vitrified for one month. Vitrified PHT grafts (n=3) and fresh PHT grafts (n=3) were orthotopically transplanted into wildtype recipient piglets. Post-operatively, recipient piglets (n=6) and unoperated positive control (n=3) underwent serial echocardiography to analyze valve size and valve function until recipients had doubled in weight. At study end-point, the hearts were explanted, immunohistochemistry and immunofluorescence analyses were performed. Linear mixed-effects models were used to model growth trajectories of Pulmonary Valve Gradient and Annulus over time. Marginal predictions and their corresponding 95% confidence intervals were derived to support model-based inference. Results: There is no statistically significant difference in the post-operative growth of gradient for vitrified cohort (Slope = 0.262 [0.113, 0.411] mmHg/day, p < 0.001) compared to fresh PHT cohort (Difference in slopes = 0.225 [-0.070, 0.521] mmHg/day, p = 0.166) and positive controls (Difference in slopes = 0.236 [-0.066, 0.538] mmHg/day, p = 0.152)). The vitrified PHT cohort showed steady valvular growth (Slope = 0.003 [-0.000, 0.006] cm/day, p = 0.095), matching fresh PHT (Difference in slopes = -0.005 [-0.010, 0.000] cm/day, p = 0.065) and positive controls (Difference in slopes = -0.002 [-0.009, 0.004] cm/day, p = 0.661). The vitrified PHTs had excellent hemodynamic function with no more than mild stenosis or regurgitation despite recipients doubling in weight. GFP mRNA was normalized to b-actin and compared to negative control pancreatic cancer cells (PA16C cell line) (p < 0.001). Conclusion: Vitrified PHTs grow at the same rate as fresh PHTs and retain viable donor cells in vivo. These findings have the potential to transform clinical practice by eliminating wait times for critically ill children.

Precision medicine has transformed oncology by tailoring treatments to the molecular and genetic characteristics of individual tumors. Stem cell-based strategies hold unique potential to complement these approaches by enabling regenerative support, targeted delivery of therapeutics, and novel models for drug screening. This review synthesizes current evidence on the integration of stem cell biology into precision cancer therapy, highlighting advances in tumor profiling, next-generation sequencing (NGS), and genome editing that enable personalized interventions. Emerging applications include engineered stem cells for selective delivery of oncolytic agents, immune modulation through stem cell-derived platforms, and the use of induced pluripotent stem cells (iPSCs) for modeling tumor heterogeneity. Advances in NGS are accelerating tumor-specific profiling, facilitating gene editing of stem cells, and refining patient selection for therapy. Despite progress, translational barriers remain, including risks of tumorigenicity, ethical concerns, high costs, immune rejection, and limited large-scale clinical validation. Stem cell-based precision oncology is a rapidly evolving field with significant promise. Future directions include integrating NGS-driven tumor profiling with engineered stem cells, optimizing safety through gene-editing technologies, and advancing clinical trials to establish efficacy. These efforts could reshape the landscape of individualized cancer care.

Research on the construction method and characterization of neutralizing mouse-canine chimeric antibody against canine distemper virus.

Lipidomics and transcriptomics analyses reveal high sperm storage ability-related lipids/genes in the liver-blood-utero-vaginal junction mucosa axis of female ducks.

Carboxymethyl chitosan/oxidized carboxymethyl starch Schiff base hydrogels containing fasudil for islet encapsulation and transplantation.

IFNγ-exosomes accelerate wound healing by suppressing immune rejection of allogeneic keratinocytes in collagen/PRP scaffolds via the IDO-kynurenine pathway

Nanotechnology is transforming the area of corneal tissue engineering by improving scaffold design and enabling sophisticated therapeutic strategies. Nanomaterials are being used to improve the corneal scaffolds' mechanical strength, permeability, and transparency, as well as to enable the therapeutic agents' targeted delivery by nanocarriers. These improvements deal with important problems in corneal repair, like inflammation, infections, and neovascularization. While corneal transplantation remains a standard treatment, the risk of rejection and availability of donor tissue are the main limitations. Recent improvements in electrospinning have made it possible to make nanofibers that look like the natural extracellular matrix (ECM). These fibers have a large surface area and high porosity, which help cells grow, stick to each other, and change into different types of cells. Both synthetic and natural polymers have been successfully employed to fabricate biocompatible and biodegradable nanofibers, indicating their potential for the treatment of various corneal disorders. Electrospun nanofibers are very useful for corneal tissue engineering because they are easy to use, can be used in surgery, and are structurally similar to the cornea. Adding nanofibers and nanoparticles to corneal tissue engineering improves the scaffold and allows for targeted therapies, which means that there are more advanced ways to reconstruct and rehabilitate the cornea. This study investigates the application of naturally derived and synthetic nanoparticles in drug delivery systems and the development of composite nanoparticles, highlighting their potential to improve corneal tissue engineering techniques.

Mesenchymal stromal/stem cells (MSCs) have introduced as a cornerstone of regenerative medicine, owing to their immunomodulatory properties and therapeutic potential in autoimmune and inflammatory disorders. Although, their clinical application is often restricted due to immune rejection and heterogeneity in immunoregulatory responses. The advent of Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR-associated protein 9 (CRISPR/Cas9) technology has revolutionized MSC engineering, enabling precise genetic modifications to enhance their immunological efficacy. This review explores how CRISPR-mediated editing of MSCs can mitigate immunogenicity, amplify anti-inflammatory functions, and repurpose MSCs for targeted immunotherapy. Key strategies include knockout of β2-microglobulin to evade T-cell recognition, augmentation of anti-inflammatory mediators like interleukin (IL)-10 and TNF-alpha stimulated gene/protein 6 (TSG-6), and disruption of pro-inflammatory pathways such as toll-like receptor 4 (TLR4)/NF-κB. In addition, CRISPR-engineered MSCs demonstrate promise in reshaping tumor microenvironments and combating bacterial infections through enhanced innate immunity. Despite challenges including off-target effects and delivery optimization, CRISPR-tailored MSCs represent a transformative approach to overcoming immunological barriers, paving the way for universal, off-the-shelf therapies in rheumatoid arthritis, cancer, and beyond.

This study presents a method for obtaining a PDL graft from the corneal stroma for subsequent clinical use (transplantation through sutureless covering of the cornea). Fifteen donor corneoscleral buttons were used, including five cryopreserved ones. In all 15 corneoscleral discs, the Descemet's membrane with endothelium had previously been peeled and transplanted during Descemet's membrane endothelial keratoplasty (DMEK). In eight discs, the Bowman's layer had also been separated and transplanted during Bowman's layer transplantation. In all cases, the PDL graft was obtained by corneal pneumodissection. The resulting grafts were preserved for further clinical use. In all 15 cases, type 1 big bubble with PDL detached from the stroma was successfully created in corneoscleral discs without the Descemet's membrane. In two cases, rupture of the big bubble and damage to the PDL occurred. In 13 cases, the PDL was successfully excised (trephined), stained, and preserved after pneumodissection for subsequent transplantation. The proposed technique does not require expensive equipment, does not increase the demand for donor tissue, fully complies with the concept of multi-transplantation, and carries a minimal risk of donor tissue rejection.

Cardiac organoids (hiPSC-COs), an emerging novel methodology, simulate human cardiac development and disease progression, providing a powerful in vitro model for cardiovascular research. This study systematically reviews the progress of translational research on cardiac organoids from laboratory to clinical applications. It focuses on two major construction strategies: first, the self-organizing differentiation based on embryoid bodies can reproduce multi-lineage cardiac structures and is suitable for studies of developmental abnormalities such as congenital heart diseases; second, the modular assembly scheme demonstrates high customizability through the precise combination of pre-differentiated cell types in constructing specific pathological models (such as arrhythmia and MI). This study further summarizes its application value in modeling heart diseases driven by environmental factors (such as cryogenic damage and hypoxia) and genetic factors, as well as in screening drug-induced cardiotoxicity. It also analyzes the potential and clinical transformation challenges, such as immune rejection and tumorigenicity, in the transplantation of iPSC-based cardiac organoids in terms of vascularization integration and recovery of electrical coupling function. Finally, this study provides a roadmap for the development of next-generation cardiac organoids for drug discovery, precision medicine, and regenerative medicine.

Tendon injuries affect millions of people globally and are among the most prevalent musculoskeletal conditions, frequently resulting in chronic pain, reduced mobility, and functional impairment. While conservative and surgical treatments are available, limitations such as low healing capacity, scar formation, and reduced biomechanics necessitate alternative approaches. Tissue engineering offers a promising solution by combining cells, scaffolds, and bioactive molecules to regenerate tendon tissue. This review presents key concepts and emerging trends, highlighting the cellular components, scaffold materials, and manufacturing processes. Tenocytes and mesenchymal stem cells are fundamental for tissue regeneration, as they synthesize extracellular matrix components and regulate inflammatory responses. Various natural and synthetic polymers have been fabricated into scaffolds that mimic the structure and biomechanics of natural tendons. Composite and hybrid scaffolds are utilized to improve the biocompatibility of natural materials with the mechanical stability of synthetic materials. Advanced technologies, such as electrospinning, freeze-drying, and 3D bioprinting, enable the creation of scaffolds with defined architecture and functional gradients, improving cell alignment, differentiation, and tendon–bone integration. Although promising preclinical data exists, major challenges remain in translating these strategies clinically, particularly vascularization, immune rejection, and mechanical stability. Continued interdisciplinary attempts in biomaterials science, cellular biology, and engineering are crucial to advancing clinically viable tendon tissue engineering.

ABSTRACTExtracellular vesicles (EVs) can cross the blood–brain barrier and enter the systemic circulation, potentially acting as peripheral biomarkers of stroke neuropathology. Here, we investigated alterations in EV RNA cargoes extracted from rat brain and plasma before and after stroke induction via middle cerebral artery occlusion and subsequent human neural stem cells (hNSCs) transplantation. EV RNA coexpression profiles were assessed, and digital source tracking was used to determine EV origin. The therapeutic effects of intra‐arterial delivery of hNSCs on ischemic rat brains were quantified, focusing on functional recovery, resolution of ischemic lesions, and the microenvironment. Stroke induced distinct EV secretion patterns, with a notable increase in EV secretion from non‐neuronal cells. hNSCs transplantation caused minimal immune rejection and transplanted cells survived in the brain for over a week. Stem cell‐derived EVs were detected in peripheral blood, indicating prolonged systemic distribution after transplantation. Gene regulatory network analyses identified specific EV miRNAs that play crucial roles in neurogenesis, wound healing, angiogenesis, and blood–brain barrier integrity. An integrated analysis of EV RNAs in brain and plasma samples revealed that stroke increased correlations in RNA expression between brain and plasma and that hNSCs transplantation reversed the effect. Brain‐ and plasma‐derived EVs carry similar molecular information after stroke, suggesting that plasma‐derived EV RNAs reflect stroke pathophysiology. Intra‐arterial transplantation of hNSCs improved outcomes after stroke in rats, by promoting endogenous neurogenesis and maintaining blood–brain barrier integrity. The identified EV miRNAs provided a new mechanism by which hNSCs transplantation regulates neural regeneration through the miR‐204‐5p/EFNB3 axis.

Acute rejection, one of the most devastating complications that can occur following organ transplantation, is caused by antigenic differences between the organ donor and the recipient. Following cardiac transplantation, an estimated 12% of patients will experience at least one episode of moderate or severe acute rejection in the first year after transplantation. To better understand the genetic mechanisms underlying acute rejection, Yucatan pigs (YP) serve as an ideal preclinical model. Translatability of the YP preclinical model relies on the fidelity observed between preclinical and clinical pathologies. Cell-free DNA (cfDNA) analysis has emerged as a blood-based, non-invasive screening tool for acute rejection of solid organs following transplantation. We present a detailed characterization of the genomic variance in YPs. The degree of variance matches that observed in humans, enabling for the ability to detect and distinguish between donor-derived and recipient-derived fragments isolated from the transplant recipient’s blood.

Background The lncRNAs associated with protein palmitoylation in breast cancer (BC) remain largely unexplored. Methods We retrieved transcriptome, proteome, and mutation data from TCGA-BRCA (BC), identified 592 palmitoylation-related lncRNAs (PRLs), constructed a prognostic model (PmPRLs) based on their characteristics. According to the score of the median risk, the “High-”and “Low” risk groups were distinguished. The predictive potential of PmPRLs for the prognosis of BC was determined through Kaplan-Meier (KM) survival analysis, ROC curve analysis, and risk scoring verification using the training set and validation set. The differences of PmPRLs in different risk groups were illustrated by using gene mutation frequency, immune function, tumour immune dysfunction and rejection (TIDE) score and drug sensitivity analysis. Based on this model, key feature LncRNAs were screened out. After the identified LncRNAs were verified by the external dataset TANRIC, a series of tumour phenotypic experiments were conducted to comprehensively demonstrate their role in tumourigenesis and development. Results We identified 2 key feature lncRNAs, AC016394.2 and AC022150.4, as the most significant prognostic factors. Both of these lncRNAs exhibited high expression levels in the TCGA and TANRIC datasets and were closely associated with tumour cell growth, proliferation, and migration. More importantly, based on co-expression analysis, we proposed that AC016394.2 and AC022150.4 may respectively regulate SEC24C and ZNF611. Furthermore, these two lncRNAs enhanced the palmitoylation modification of these proteins. Conclusion The insights regarding the potential roles of AC016394.2 and AC022150.4 can enhance our understanding of the mechanisms towards the pathogenesis and progression of BC.

Kidney transplantation remains the optimal treatment for end-stage renal disease, yet faces persistent challenges including organ shortages and risk of infection due to systemic immunosuppression. Cell therapy is expected to replace immunosuppressive agents. However, while Treg cell therapy can mitigate immune rejection, it fails to significantly prolong graft survival because peripherally induced Treg cells exhibit transdifferentiation potential in the circulatory system. Recent advances in nanocarrier systems offer promising approaches for achieving graft-specific immune tolerance. Through single-cell sequencing analysis, CD248 is identified as a pivotal stromal cell marker in renal allograft rejection, modulated by HIF-1α and IL-1β signaling pathways. Leveraging macrophage membrane coating technology, nanoparticles co-loaded is developed with IL-2 and TGF-β expressing plasmids. These nanoparticles incorporate a CD248-targeting antibody (IgG78) and plasmids containing a kidney-specific NPHS2 promoter, enabling dual-targeting capability for localized gene expression. In vitro validation demonstrated efficient differentiation of CD4⁺T cells into functional Treg populations. In rat renal transplantation models, nanoparticle treatment increased Treg cells in the graft and significantly prolonged allograft survival, improved renal function, and attenuated complement deposition. The findings establish a targeted nanoparticle platform that promotes graft-specific immune tolerance through localized Treg cell expansion, potentially reducing dependence on systemic immunosuppression.

Stem cell-free therapy for healthy brain aging: Mechanisms, challenges, and prospects.