Immune Rejection Research Articles

Xenotransplantation: future frontiers and challenges.

Recent advancements in genetic engineering have propelled the field of xenotransplantation from preclinical models to early compassionate use cases. As first-in-human clinical trials (FIHCTs) approach, we examine recent developments, ethical and regulatory challenges, immunological considerations, and the clinical infrastructure necessary for successful xenotransplantation trials. Expanded access transplants of pig hearts, kidneys, and livers have identified key challenges. Heart xenotransplants revealed risks of antibody-mediated rejection and zoonotic infections, while kidney xenotransplants suggest that patient selection, rather than immune rejection, may have caused failures. While there has been a report of auxiliary liver transplantation conducted abroad, profound thrombocytopenia poses an obstacle. As FIHCTs draw near, critical clinical challenges include determining the optimal donor genetic constructs and immunosuppressive regimens. Enrollment criteria and patient selection pose additional complexity, alongside ethical concerns such as lifelong zoonosis monitoring. Only a limited number of centers have the expertise needed to conduct these complex trials. Xenotransplantation holds great promise as a solution to organ shortages, but success in FIHCTs will require careful design, multidisciplinary collaboration, and strong infrastructure. Addressing immunologic, ethical, and patient selection challenges will be critical. With proper preparation, xenotransplantation could transform organ transplantation.

Endogenous Protein-Modified Gold Nanorods as Immune-Inert Biomodulators for Tumor-Specific Imaging and Therapy.

Engineered modifications of nanomaterials inspired by nature hold great promise for disease-specific imaging and therapies. However, conventional polyethylene glycol modification is limited by immune system rejection. The manipulation of gold nanorods (Au NRs) modified by endogenous proteins (eP@Au) is reported as an engineered biomodulator for enhanced breast tumor therapy. The results show that eP@Au NRs neither activate inflammatory factors in vitro nor elicit rejection of immune responses in vivo. Tumor-specific eP@Au NRs exhibit a dual-modal imaging capability and trigger a mild photothermal effect under near-infrared light irradiation, enabling highly efficient imaging and therapy of tumors. Transcriptome sequencing and confirmatory experiments reveal that the antitumor effect is mainly attributed to the repression of PI3K-Akt/MAPK signaling pathways at the molecular level. This powerful and surprising in situ eP-regulated biomodulation demonstrates the advantages of convenient fabrication, inert immunogenicity, and biocompatibility, providing an alternative strategy for biomedical imaging and therapy.

Evaluation of efficacy and safety of generic tacrolimus (Suprotac®) compared to reference tacrolimus (Prograf®) in kidney transplantation: a phase IV study.

Transplant recipients are given an immunosuppressive regimen such as tacrolimus to prevent organ rejection. Suprotac® is a generic tacrolimus that is utilized in kidney transplantation regimen in Iran. This post-market study was conducted to evaluate the safety and efficacy of Suprotac® in comparison with Prograf®. In this two-armed, open-label, parallel, active-controlled, and cohort study, de novo kidney transplant recipients aging 18 to 65 years were prescribed Suprotac® or Prograf® as part of the immunosuppressant protocol. The primary outcome was comparing the mean estimated glomerular filtration rate (eGFR) at month 12. The secondary outcomes were the assessment of patient and graft survival, acute rejections during hospitalization, tacrolimus dose, trough concentration, and trough concentration/dose (C/D) ratio, and adverse events (AEs) during the study period. A total of 201 patients were enrolled in this study. At discharge, the eGFR was lower in the Suprotac® group compared to the Prograf® group (51.70 ml/min/1.73m2 and 57.48 ml/min/1.73m2, respectively; p = 0.042). However, at month 12, there was no significant difference in mean eGFR between the two groups (58.94 ml/min/1.73m2 and 59.78 ml/min/1.73m2, respectively; p = 0.772). Other outcomes, including patient and graft survival, acute rejection during hospitalization, tacrolimus dose, trough concentration, and C/D ratio, and overall incidence of AEs were similar between the two groups (p > 0.05). The efficacy and safety profile of the generic tacrolimus were shown to be comparable to the reference tacrolimus at month 12.

Molecular and cellular morphology of placenta unveils new mechanisms of reproductive immunology.

Despite of numerous studies of the placenta, some molecular and cellular characteristics, particularly the relationship among different cell types, have not been well understood. We aim to investigate the basic and intricate details of cellular and molecular elements in early and late phase placentas to gain better understanding of the immune regulation of human reproductive process. A novel combination of techniques of spatial transcriptomics(ST), multiple immunohistochemistry, and a dual labeling combining immunohistochemistry and (fluorescence in situ hybridization) FISH on normal and ectopic pregnancy and animal models was employed to investigate the placenta at tissue, cell, protein and molecular levels and to trace the fetal and maternal origin of every cell in early and late placentas. Original discoveries include early expression of immune checkpoint proteins in embryo trophoblasts even before implantation. The detailed distributional relationships among different cell types of fetal and maternal origins in placenta and decidua indicate an immune rejection of the mother towards the fetus and this was counterbalanced by immune inhibitory proteins and blocking antibody Immunoglobulin G4 (IgG4) at the junction between the fetus and the mother. In contrary to common believe, we found that vascular endothelial and glandular epithelial cells in the decidua remain maternal in origin and were not replaced by fetal cells. At term placenta, fetal immune cells infiltrated into the maternal side of the decidus and vice versa indicating a possible immune reaction between fetal and maternal immune systems and suggesting a possible immune mechanism for trigger of parturition. The ability of trophoblasts to create an immune suppressed environment was also supported by findings in ectopic pregnancy and the animal models. The findings indicate a fetus-driven mechanism of immune balance involving both cellular and humoral immunity in human reproduction.

Selective Tissue Penetration of the Corneal Layers of Cyclosporin 2% Associated with Miglyol in Rabbits.

Purpose: Cyclosporin A (CsA) is a drug used to prevent immune rejection in corneal transplantation. Most grafts performed today are endothelial grafts which are complicated with poor penetration of CsA into the endothelium due to its hydrophobicity. To improve CsA penetration into the corneal a new ocular formulation of CsA 2% with Miglyol was developed and is commercially available. The purpose of this pharmacokinetic study was to determine the concentrations of CsA in all layers of the cornea, in particular in the endothelium after topical administration of CsA 2%-Miglyol in rabbits. Methods: Sixteen rabbits were divided in 4 groups according to the time from the last instillation of CsA 2%-Miglyol to corneal sampling. Rabbit eyes received one drop of CsA twice a day for 5 days. Corneal tissue and plasma samples were collected at 2, 6, 12, and 24 h. CsA concentrations were measured using liquid chromatography-tandem mass spectrometry method. Results: Maximum concentrations (Cmax) of CsA were obtained in corneal tissues within 2 h after the last instillation of CsA 2%-Miglyol, except in the endothelium (12 h). Cmax were 59.75 ± 12.09 ng/mg, 15.66 ± 4.31 ng/mg, 5.17 ± 0.88 ng/mg, and 2.65 ± 0.47 ng/mg for the epithelium, endothelium, anterior stroma and posterior stroma. CsA concentrations remained high over a 24-h in all corneal layers. Conclusions: The topical application of CsA 2%-Miglyol allowed a high concentration of CsA in the corneal endothelium. The good penetration of CsA into the endothelium suggests that this formulation can be effective to prevent endothelial graft rejection.

Safety, efficacy, and immunogenicity of a novel IgG degrading enzyme (KJ103): results from two randomised, blinded, phase 1 clinical trials.

The approved intravenous adeno-associated virus (AAV) therapies are limited by the widespread prevalence of pre-existing anti-AAV antibodies in the general population, which are known to restrict patients' ability to receive gene therapy and limit transfection efficacy in vivo. To address this challenge, we have developed a novel recombinant human immunoglobulin G degrading enzyme KJ103, characterized by low immunogenicity and clinical value for the elimination of anti-AAV antibodies in gene transfer. Herein, we conducted two randomized, blinded, placebo-controlled, single ascending dose Phase I studies in China and New Zealand, to evaluate the pharmacokinetics, pharmacodynamics, safety and immunogenicity of KJ103 in healthy volunteers. The results confirmed that KJ103 rapidly reduced IgG and maintained plasma IgG at low levels for one week. Dose of KJ103 ranging from 0.01 to 0.40 mg/kg had a favorable safety and tolerability profile across diverse ethnic and gender groups. KJ103 demonstrated a lower incidence of pre-existing anti-drug antibodies (ADAs) compared to currently approved human IgG degrading enzyme Imlifidase, with most induced ADAs predominantly reverting to baseline six months after administration. These properties are ideal for the management of immune disorders, rejection responses, and immunotherapies where pre-existing antibodies can reduce efficacy. Furthermore, we tested AAV2 neutralizing antibodies to confirm the potential utility of KJ103 in enhancing gene therapy.

Xenographic lenticule implantation followed by riboflavin and UV treatment: A promising alternative for corneal ectasias management.

The cornea is the primary refracting surface of the eye, requiring precise curvature to ensure optimal vision. Any distortion in its shape may result in significant visual impairment. Corneal ectasias, such as keratoconus (KC), is characterized by gradual thinning and protrusion of the thinned area, due to biomechanical weakening of the tissue, leading to astigmatism and vision loss. KC affects approximately 1 in 2000 individuals globally. While corneal transplantation is the main treatment, limited donor availability and potential immunogenic reactions have spurred the search for alternatives. Stromal lenticule implantation using decellularized porcine corneas offers a promising solution, with reduced immunogenicity and risk of rejection. Additionally, combining this approach with riboflavin and UV radiation treatment post-surgery enhances collagen fibril cross-linking, promoting tissue integration and organization. This study evaluated the efficacy of heterologous transplantation of decellularized porcine lenticules into the corneal stroma of rabbits, followed by riboflavin application and UV radiation. Results demonstrated increased stromal thickness and no signs of tissue rejection, indicating minimal immunogenicity of the lenticules. The cross-linking technique successfully improved tissue organization, suggesting that xenographic lenticule implantation, combined with riboflavin and UV light, is a promising alternative for treating corneal ectasias like KC. Further research is necessary to confirm the long-term efficacy and safety of this method in human subjects.

Research on the application of CRISPR technology in the treatment of type 1 diabetes (T1D)

Diabetes is a chronic disease with a rapid increase in incidence, which is a general problem around the world. Two main types of diabetes are included. Polygenic diabetes includes type 1 diabetes (T1D) and type 2 diabetes (T2D), and their monogenic forms are juvenile mature diabetes (MODY) and neonatal diabetes (NDM). CRISPR technology is a gene therapy technology with low cost but very high feasibility. At present, researchers have envisioned the use of CRISPR technology in the treatment of T1D, but this technology has a high off-target rate, immune rejection and no abundant clinical trials in the human body to verify this technology, resulting in the fact that this technology is not really used in clinical treatment. In the middle. This article mainly analyzes and summarizes the problems and solutions encountered by CRISPR-cas9 technology from basic theory to idealized models. This article provides new solutions for the treatment of T1D with CRISPR technology and also provides references for this technology. In addition, problems such as immune rejection in the human body have not been solved. Future research can focus on the solution to the problem of the suppression of cellular immune rejection after treatment and the impact of re-mutation.

Advances in the Application of CRISPR-Cas9 in Stem Cell Therapy

Stem cell research has advanced rapidly, offering promising treatments for refractory diseases due to their unique capabilities for self-renewal and pluripotent differentiation. Stem cells play pivotal roles in treating genetic disorders, neurodegenerative diseases (NDDs), cardiovascular conditions, and cancer. In genetic diseases, combining stem cells with gene-editing tools like CRISPR-Cas9 enables precise correction of pathogenic genes, while healthy stem cells repair tissue by replacing diseased cells. For NDDs, iPSCs can differentiate into dopaminergic neurons to replace damaged brain cells and enhance neural regeneration. In cardiovascular diseases, they promote myocardial and vascular repair. In cancer, stem cells boost anti-tumor immunity and deliver drugs directly to tumor sites, improving treatment efficacy. Despite these breakthroughs, challenges persist. High-quality stem cell production is limited, and controlling differentiation to prevent tumorigenesis remains critical. Allogeneic transplants risk immune rejection, and using embryonic stem cells raises ethical concerns. Regulatory frameworks and clinical standards are needed to ensure safety and efficacy, alongside addressing ethical and patient rights issues. With continued innovation, stem cell therapy is going to revolutionize medicine, offering novel methods for complex diseases and improving global health

Human leukocyte antigen and donor-specific antibodies in liver transplantation.

In this article, we comment on an article published in a recent issue of the World Journal of Gastroenterology. We specifically focus on the roles of human leukocyte antigen (HLA) and donor-specific antibodies (DSAs) in pediatric liver transplantation (LT), as well as the relationship between immune rejection after LT and DSA. Currently, LT remains the standard of care for pediatric patients with end-stage liver disease or severe acute liver failure. However, acute and chronic rejection continues to be a significant cause of graft dysfunction and loss. HLA mismatch significantly reduces graft survival and increases the risk of acute rejection. Among them, D→R one-way mismatch at three loci was significantly related to graft-versus-host disease incidence after LT. The adverse impact of HLA-DSAs on LT recipients is already established. Therefore, the evaluation of HLA and DSA is crucial in pediatric LT.

Extracellular vesicles: essential agents in critical bone defect repair and therapeutic enhancement.

Bone serves as a fundamental structural component in the body, playing pivotal roles in support, protection, mineral supply, and hormonal regulation. However, critical-sized bone injuries have become increasingly prevalent, necessitating extensive medical interventions due to limitations in the body's capacity for self-repair. Traditional approaches, such as autografts, allografts, and xenografts, have yielded unsatisfactory results. Stem cell therapy emerges as a promising avenue, but challenges like immune rejection and low cell survival rates hinder its widespread clinical implementation. Extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) have garnered attention for their regenerative capabilities, which surpass those of MSCs themselves. EVs offer advantages such as reduced immunogenicity, enhanced stability, and simplified storage, positioning them as a promising tool in stem cell-based therapies. This review explores the potential of EV-based therapy in bone tissue regeneration, delving into their biological characteristics, communication mechanisms, and preclinical applications across various physiological and pathological conditions. The mechanisms underlying EV-mediated bone regeneration, including angiogenesis, osteoblast proliferation, mineralization, and immunomodulation, are elucidated. Preclinical studies demonstrate the efficacy of EVs in promoting bone repair and neovascularization, even in pathological conditions like osteoporosis. EVs hold promise as a potential alternative for regenerating bone tissue, particularly in the context of critical-sized bone defects, offering new avenues for effective bone defect repair and management.

The potency of aloe emodin‐loaded nanoparticles in conjunction with IFN‐γ for the pretreatment of mesenchymal stem cells with class II transactivator silence to alleviate severe acute pancreatitis

AbstractMesenchymal stem cells (MSCs) have a moderate impact on the therapy of severe acute pancreatitis. This study seeks to improve the therapeutic effectiveness of MSCs. By preconditioning them via the upregulation of critical anti‐inflammatory molecules, so diminishing immune rejection, we are creating a path for more effective treatments. Aloe emodin (AE), a natural active monomer with low‐toxicity, in conjunction with interferon gamma (IFN‐γ) (I‐AE), markedly upregulated immunosuppressive molecules indoleamine 2,3‐dioxygenase and programmed cell death‐Ligand 1 in MSCs, thereby pharmacologically modulating the inhibition of CD4 − T cell activation in vitro effectively. Transient transfection of small interfering RNA silenced the class II transactivator (CIITA) gene expression of umbilical cord mesenchymal stem cells (UMSCs) interfering with human leukocyte antigen class II expression to avert immune rejection. AE‐loaded nanoparticles efficiently maintained proliferation inhibition of MSCs within a manageable range by sustained release. UMSCs pretreated by I‐AE with CIITA silencing preserved pancreatic structure as evidenced by diminished acinar cell death, reduced pancreatic edema and inflammation, and significantly lowered serum amylase levels The encouraging potential of UMSCs with CIITA gene silencing combined with AE and IFN‐γ pretreatment offers optimism for clinical application in pancreatitis therapy.

Transcriptomic and Functional Landscape of Adult Human Spinal Cord NSPCs Compared to iPSC-Derived Neural Progenitor Cells.

The adult human spinal cord harbors diverse populations of neural stem/progenitor cells (NSPCs) essential for neuroregeneration and central nervous system repair. While induced pluripotent stem cell (iPSC)-derived NSPCs offer significant therapeutic potential, understanding their molecular and functional alignment with bona fide spinal cord NSPCs is crucial for developing autologous cell therapies that enhance spinal cord regeneration and minimize immune rejection. In this study, we present the first direct transcriptomic and functional comparison of syngeneic adult human NSPC populations, including bona fide spinal cord NSPCs and iPSC-derived NSPCs regionalized to the spinal cord (iPSC-SC) and forebrain (iPSC-Br). RNA sequencing analysis revealed distinct transcriptomic profiles and functional disparities among NSPC types. iPSC-Br NSPCs exhibited a close resemblance to bona fide spinal cord NSPCs, characterized by enriched expression of neurogenesis, axon guidance, synaptic signaling, and voltage-gated calcium channel activity pathways. Conversely, iPSC-SC NSPCs displayed significant heterogeneity, suboptimal regional specification, and elevated expression of neural crest and immune response-associated genes. Functional assays corroborated the transcriptomic findings, demonstrating superior neurogenic potential in iPSC-Br NSPCs. Additionally, we assessed donor-specific influences on NSPC behavior by analyzing gene expression and differentiation outcomes across syngeneic populations from multiple individuals. Donor-specific factors significantly modulated transcriptomic profiles, with notable variability in the alignment of iPSC-derived NSPCs to bona fide spinal cord NSPCs. Enrichment of pathways related to neurogenesis, axon guidance, and synaptic signaling varied across donors, highlighting the impact of genetic and epigenetic individuality on NSPC behavior.

Advancements and Challenges in Immune Protection Strategies for Islet Transplantation.

Pancreatic islet transplantation is a crucial treatment for managing type 1 diabetes (T1D) in clinical settings. However, the limited availability of human cadaveric islet donors and the need for ongoing administration of immunosuppressive agents post-transplantation hinder the widespread use of this treatment. Stem cell-derived islet organoids have emerged as an effective alternative to primary human islets. Nevertheless, implementing this cell replacement therapy still requires chronic immune suppression, which may result in life-long side effects. To address these challenges, innovations such as encapsulation devices, universal stem cells, and immunomodulatory strategies are being developed to mitigate immune rejection and prolong the function of the transplant. This review outlines the contemporary challenges in pancreatic β cell therapy, particularly immune rejection, and recent progress in immune-isolation devices, hypoimmunogenic stem cells, and immune regulation of transplants. A comprehensive evaluation of the advantages and limitations of these approaches will contribute to improved future clinical investigations. With these promising advancements, the application of pancreatic β cell therapy holds the potential to effectively treat T1D and benefit a larger population of T1D patients.

Polydopamine-Induced BMP7-Poly (Lactic-Co-Glycolic Acid)-Nanoparticle Coating Facilitates Osteogenesis in Porous Tantalum Scaffolds.

Bone defects are difficult to treat clinically and most often require bone grafting for repair. However, the source of autograft bone is limited, and allograft bone carries the risk of disease transmission and immune rejection. As tissue engineering technology advances, bone replacement materials are playing an increasingly important role in the treatment of bone defects. Porous tantalum (PT) scaffolds have shown beneficial clinical effects in the repair of bone defects, surface modification of PT to induce osteogenic differentiation of mesenchymal stem cells (MSC) is the key to optimizing this material. Poly (lactic-co-glycolic acid) nanoparticle (PLGA NPs) encapsulating bone morphogenetic protein 7 (BMP7) (BPNPs) was prepared by a double emulsion (water/oil/water [W/O/W]) method and adhered on polydopamine (PDA)-coated PT (PPT) that was prepared by biomimetic method to prepare BPNPs-coated PPT (BPPT). The successful preparation of BPPT was monitored by scanning electron microscopy (SEM) and energy spectrum. Murine calvarial preosteoblasts (MC3T3-E1) cells were co-cultured with BPPT, vitro experiments showed that BPPT promoted cell proliferation and osteogenic differentiation. BPPT was further implanted into the bone defect of the distal femoral epiphysis of the rabbit. At 4 weeks postoperatively, in the BPPT group, high-resolution CT reconstruction indicated that bone volume/total volume (BV/TV) was near 50%, and the hard tissue section indicated that the depth of new bone ingrowth into the scaffolds was nearly 2 mm. The immunofluorescence staining of bone tissue around the bone defects indicated that the expression of osteogenic-related proteins was higher in the BPPT group than the other groups. Taken together, our results suggest that BPPT promoted early osteointegration, which may provide a novel approach for the clinical treatment of bone defects.

Superior mechanical properties of an additively manufactured gradient lattice structure through FEM simulation and in-situ compression tests

Currently, the increasing incidence of bone defects and damage due to diseases and trauma, the treatment of bone defects usually uses autologous bone graft or allogeneic bone graft, however, the amount of autologous bone is limited, and there is also the risk of infection at the site of bone extraction, and allogeneic bone graft also faces problems such as disease transmission and immune rejection. In summary, artificial bone provides a new option for patients. This study investigates the mechanical properties of homogeneous and gradient Gyroid and Diamond porous structures, designed with average porosities of 50%, 60%, and 70%, using triply-periodic minimal surface models for artificial joints. Finite Element Method simulations and compression tests were employed to characterize the mechanical properties of Ti6Al4V porous scaffolds fabricated using the selective laser melting technique. The measured elastic modulus of the scaffolds ranged from 6.24 to 10.5GPa, meeting the requirements for orthopedic implants. Gyroid structures were shown to exhibit superior nominal stiffness compared to Diamond structures at equivalent porosity levels. Furthermore, the linear gradient porous structures demonstrated significantly higher elastic modulus, yield strength, and compressive strength compared to homogeneous porous structures, with increases of 66.9%, 20.3%, and 16.5%, respectively. The energy absorption capacity of the linear gradient porous structure was also found to be 3.3-fold greater than that of the homogeneous structure.The lightweight design of this linear gradient porous structure provides the basis for bone implants for biomedical applications.

Development of a Novel Prognostic Model for Lung Adenocarcinoma Utilizing Pyroptosis-Associated LncRNAs.

Lung cancer is a highly prevalent and fatal cancer that seriously threatens the safety of people in various regions around the world. Difficulty in early diagnosis and strong drug resistance have always been difficulties in the treatment of lung cancer, so the prognosis of lung cancer has always been the focus of scientific researchers. This study used genotype-tissue expression (GTEx) and the cancer genome atlas (TCGA) databases to obtain 477 lung adenocarcinoma (LUAD) and 347 healthy individuals' samples as research subjects and divided LUAD patients into low-risk and high-risk groups based on prognostic risk scores. Differentially expressed gene (DEG) analysis was performed on 25 pyroptosis-related genes obtained from GeneCards and MSigDB databases in cancer tissues of LUAD patients and noncancerous tissues of healthy individuals, and seven genes were significantly different in cancer tissues and noncancerous tissues among them. Coexpression analysis and differential expression analysis of these genes and long noncoding RNAs (lncRNAs) found that three lncRNAs (AC012615.1, AC099850.3, and AO0001453.2) had significant differences in expression between cancer tissues and noncancerous tissues. We used Cox regression and the least absolute shrinkage sum selection operator (LASSO) regression to construct a prognostic model for LUAD patients with these three pyroptosis-related lncRNAs (pRLs) and analyzed the prognostic value of the pRLs model by the Likaplan-Meier curve and Cox regression. The results show that the risk prediction model has good prediction ability. In addition, we also studied the differences in tumor mutation burden (TMB), tumor immune dysfunction and rejection (TIDE), and immune microenvironment with pRLs risk scores in low-risk and high-risk groups. This study successfully established a LUAD prognostic model based on pRLs, which provides new insights into lncRNA-based LUAD diagnosis and treatment strategies.

Patterns of belatacept use and risk of post-transplant lymphoproliferative disorder in US kidney transplant recipients: An analysis of the Organ Procurement and Transplantation Network database.

Belatacept is approved for the prophylaxis of organ rejection in Epstein-Barr virus (EBV)-seropositive kidney transplant recipients and is associated with a risk of post-transplant lymphoproliferative disorder (PTLD). Data from the Organ Procurement and Transplantation Network were used to examine patterns of belatacept use, describe patient characteristics, and estimate risk of PTLD in EBV-seropositive, kidney-only transplant recipients receiving belatacept- or calcineurin inhibitor (CNI)-based immunosuppression as part of US Food and Drug Administration-mandated safety monitoring. During the study period (June 15, 2011-June 14, 2016), 94.9% (1631/1719) of belatacept-treated and 89.7% (59,992/66,905) of CNI-treated patients with known EBV serostatus were EBV seropositive. Among EBV-seropositive patients, 50.2% (belatacept) and 56.8% (CNI) received a standard criteria donor kidney, 59.5% and 18.7% received basiliximab induction, and 22.9% and 50.8% received antithymocyte globulin induction. PTLD developed in nine belatacept-treated patients (two with central nervous system [CNS] involvement) and 225 CNI-treated patients (nine with CNS involvement). Four and 81 patients, respectively, died due to PTLD. Kaplan-Meier analysis did not show a significant between-group difference in PTLD estimated incidence rates within 5 years (0.70% versus 0.48%, respectively; p = 0.18). Additionally, estimated PTLD incidence was not significantly different between treatment groups in a propensity score matched cohort. The majority of adult kidney-only transplant recipients treated with belatacept in routine clinical practice are EBV seropositive. In this study, the risk of PTLD in these patients, while higher than for CNI-based immunosuppression, remained low after adjusting for differences in patient characteristics. These studies are registered at ClinicalTrials.gov: NCT01670058 and NCT01656343.

The impact of artificial intelligence and machine learning in organ retrieval and transplantation: A comprehensive review.

This narrative review examines the transformative role of Artificial Intelligence (AI) and Machine Learning (ML) in organ retrieval and transplantation. AI and ML technologies enhance donor-recipient matching by integrating and analyzing complex datasets encompassing clinical, genetic, and demographic information, leading to more precise organ allocation and improved transplant success rates. In surgical planning, AI-driven image analysis automates organ segmentation, identifies critical anatomical features, and predicts surgical outcomes, aiding pre-operative planning and reducing intraoperative risks. Predictive analytics further enable personalized treatment plans by forecasting organ rejection, infection risks, and patient recovery trajectories, thereby supporting early intervention strategies and long-term patient management. AI also optimizes operational efficiency within transplant centers by predicting organ demand, scheduling surgeries efficiently, and managing inventory to minimize wastage, thus streamlining workflows and enhancing resource allocation. Despite these advancements, several challenges hinder the widespread adoption of AI and ML in organ transplantation. These include data privacy concerns, regulatory compliance issues, interoperability across healthcare systems, and the need for rigorous clinical validation of AI models. Addressing these challenges is essential to ensuring the reliable, safe, and ethical use of AI in clinical settings. Future directions for AI and ML in transplantation medicine include integrating genomic data for precision immunosuppression, advancing robotic surgery for minimally invasive procedures, and developing AI-driven remote monitoring systems for continuous post-transplantation care. Collaborative efforts among clinicians, researchers, and policymakers are crucial to harnessing the full potential of AI and ML, ultimately transforming transplantation medicine and improving patient outcomes while enhancing healthcare delivery efficiency.

Stem cell treatment for dry AMD

Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss worldwide, affecting a significant proportion of the aging population. While wet AMD can be treated with anti-vascular endothelial growth factor injections, there is very little that can be offered to patients with dry AMD. This paper provides a review of AMD pathogenesis, current treatment methods for dry AMD, and the potential of cell-based therapies, particularly in the context of retinal pigment epithelium (RPE) replacement. AMD pathogenesis involves the formation of drusen impacting the health of the RPE. Aging, smoking, and genetic factors contribute to RPE dysfunction, leading to the progression of AMD. Newer therapies for dry AMD, including pegcetacoplan and avacincaptad pegol, mainly focus on reducing ongoing inflammation and addressing issues with complement regulation. This review discusses the emerging field of RPE replacement therapies, emphasizing the potential of induced pluripotent stem cells. Clinical trials involving RPE replacement therapy are discussed, showcasing ongoing efforts to develop effective treatments for dry AMD. While challenges, including immune rejection and integration issues, have to be solved, the potential benefits of RPE transplantation, either as cell suspensions or patches, remain significant. In conclusion, this paper highlights the promising prospects and challenges related to stem cell science in treating dry AMD, potentially marking a significant breakthrough in managing a previously untreatable disease.