Search Results (280)

Background/Objectives: There is a critical disparity between donor organs and recipients awaiting liver transplantation. Normothermic machine perfusion (NMP) has emerged as a promising strategy with which to address this shortage. This study aimed to evaluate the association between NMP and short-term outcomes following liver transplantation using a large, multivariable-adjusted national dataset. Methods: A retrospective analysis of the de-identified United Network for Organ Sharing (UNOS) database was conducted for adult liver transplant recipients between January 2020 and July 2024. Standard and deceased donor data were merged according to donor identification number. Multivariable logistic and Cox regression models were used to evaluate patient mortality, graft failure, and hospital length of stay (LOS). Results: Among 34,115 patients, adjusted regression demonstrated lower one-year patient mortality (OR 0.68, CI 0.54–0.86, p = 0.001) and graft failure (OR 0.72, CI 0.60–0.87, p = 0.001) with NMP compared to static cold storage. NMP was also associated with reduced 30-day (OR 0.67, CI 0.47–0.95, p = 0.03) and 90-day mortality (OR 0.72, CI 0.54–0.94, p = 0.02) and shorter LOS (HR 1.06, CI 1.01–1.12, p = 0.02). Kaplan–Meier and Cox analyses showed no significant differences in overall patient mortality or graft failure. Conclusions: NMP was associated with improved short-term survival in time-independent analysis; however, it failed to reach significance in time-dependent Cox regression. These findings suggest that NMP could play a role in improving short-term outcomes and expanding the donor pool for liver transplant candidates. Additional studies are needed to fully elucidate the impact of NMP on short-term survival outcomes. Full article

The rising prevalence of chronic kidney disease represents a major global health burden. Limitations of current renal replacement therapies, including donor organ shortages, rejection, and dialysis-related complications, underscore the need for innovative treatment options. This narrative review assesses the feasibility of bioengineered kidneys as an alternative to current treatments by discussing advances in decellularization, recellularization, and the transplantation of cell-on-scaffold kidneys. We propose that the development of functional bioengineered kidneys follows a hierarchical, staged process, in which vascular patency is the primary prerequisite for graft survival, followed by partial restoration of glomerular filtration, with complete tubular function remaining the final and most challenging milestone. Perfusion-based whole-organ decellularization has made significant progress in preserving the extracellular matrix, enabling the production of acellular human kidney scaffolds. However, complete recellularization of whole kidneys has not yet been achieved. Nevertheless, partially repopulated kidney scaffolds have been shown to withstand physiological blood pressure, produce urine, and exhibit filtration in large-animal models. Complete endothelial coverage of the vascular network proved essential for preventing thrombosis after transplantation. Current work on bioengineered kidneys shows promising results regarding feasibility for clinical application. It is important to note that most of the included studies are proof-of-concept, characterized by small sample sizes and short observation periods. Although these findings are crucial for further research, they cannot be generalized, and larger trials are recommended. In addition to cell-on-scaffold kidneys, 3D bioprinting is a promising technique that could eliminate the need for donor scaffolds. Full article

The corneal endothelium is essential for maintaining corneal transparency through active fluid transport and barrier function. Corneal cell loss from disease, ageing or surgical trauma underlies a significant proportion of corneal blindness worldwide, with Fuchs’ endothelial corneal dystrophy (FECD) and pseudophakic bullous keratopathy (PBK) representing the dominant clinical indications for corneal transplantation. While Descemet’s membrane endothelial keratoplasty (DMEK) has substantially improved surgical outcomes, the procedure remains constrained by global donor tissue shortage. Regenerative medicine offers a compelling alternative by exploiting the latent proliferative and reparative potential of corneal endothelial progenitor populations. This review synthesises current knowledge on the foundational biology of corneal endothelial progenitor populations and the optimisation of expansion platforms to emerging preclinical and clinical evidence for both cell-based and pharmacological regenerative strategies. We also consider the outstanding translational challenges of potency standardisation, GMP-compliant manufacturing and regulatory navigation, as well as the longer-term potential of biomaterial-cell platforms and personalised iPSC-based medicine. The cumulative evidence positions progenitor-based approaches as viable and increasingly well-characterised alternatives to conventional donor transplantation, although their routine clinical use awaits the optimisation of manufacturing and regulatory platforms. Full article

Corneal blindness remains a major cause of visual impairment worldwide and may result from trauma, infectious keratitis, degenerative disorders, endothelial dysfunction, and limbal stem cell deficiency (LSCD). Although corneal transplantation remains the standard treatment for advanced disease, its effectiveness is limited by donor tissue shortage, immune-mediated rejection, postoperative complications, and progressive graft failure. These limitations have accelerated interest in regenerative approaches aimed at restoring native corneal structure and function. Induced pluripotent stem cells (iPSCs) have emerged as a promising platform for corneal regeneration because of their pluripotency, self-renewal capacity, and potential for autologous or immune-compatible therapy. Recent advances in differentiation protocols have enabled the generation of corneal epithelial-like cells, stromal keratocyte-like cells, and corneal endothelial-like cells from iPSCs. Preclinical studies have demonstrated encouraging improvements in corneal transparency, epithelial restoration, fibrosis reduction, and endothelial function, while early clinical investigations, particularly in LSCD, have reported favorable short-term safety and functional outcomes. However, major translational barriers remain, including tumorigenicity, immunogenicity, genomic instability, manufacturing complexity, scalability, and long-term safety concerns. Stromal regeneration also remains comparatively underdeveloped relative to epithelial and endothelial applications. This review summarizes current differentiation strategies, biological mechanisms, preclinical and early clinical evidence, and the principal translational challenges associated with iPSC-based corneal regeneration. Overall, iPSC-derived corneal therapies demonstrate considerable regenerative potential, although further standardization, long-term safety evaluation, and multicenter clinical validation remain necessary before widespread clinical adoption. Full article

Corneal blindness remains a major clinical challenge, yet donor grafts are scarce. Bioprinting has emerged in recent decades to potentially overcome donor shortage. In bioprinting, collagen is a common biomaterial. However, one alternative biomaterial, which has shown promising results in corneal tissue engineering, is keratin. Therefore, human hair keratin was investigated in this study as a bioink component for stroma bioprinting. Two keratin preparations, an aqueous extraction and an alkaline extraction, were incorporated into a methacrylated hyaluronic acid bioink and compared with a collagen methacrylated hyaluronic acid bioink. Corneal stroma-like constructs were printed by extrusion bioprinting and evaluated for optical transmission, biomechanical properties, cell compatibility and protein expression of collagen type I and alpha-smooth muscle actin over a four-week period. Two different cell types, immortalized corneal keratocytes and human corneal fibroblasts, were used. The alkaline keratin dialysate-supplemented bioink showed similar optical transparency and biomechanical properties to the collagen-supplemented bioink. Cell viability was high in all formulations. Protein expression of collagen type I and α-smooth muscle actin remained low in all bioinks. Human corneal fibroblasts appeared to be in a quiescent state and were unable to produce large amounts of collagen. This comparative study between collagen and keratin is a first step towards establishing keratins in bioprinting, leading to more complex bioinks. Full article

Corneal endothelial dysfunction is a major cause of corneal blindness worldwide. This is primarily due to the limited regenerative capacity of human corneal endothelial cells (CECs) and the global shortage of donor tissues. Corneal endothelial cell therapy (CECT), which involves injecting cultured CECs into the anterior chamber, has emerged as a promising alternative to conventional transplantation. However, its clinical efficacy remains limited by several factors, including rapid cell loss, non-uniform distribution, and insufficient long-term adhesion following injection. Recent advances in biomaterials and regenerative engineering have led to the development of emerging biomaterial-assisted strategies aimed at addressing these challenges. In this review, we provide a mechanistic and translational overview of next-generation CECT, highlighting a range of biomaterial-assisted strategies aimed at improving cell retention, spatial localization, and long-term adhesion following injection. These emerging approaches aim to mitigate key limitations of conventional cell injection therapy, including variability in cell distribution and retention. However, their effectiveness and translational feasibility remain under active investigation. In addition, we analyze recent global patent trends, regulatory frameworks, and market dynamics to highlight emerging opportunities for innovation and development in this field. Although many of these technologies remain at the preclinical or early translational stage, these approaches may provide a promising direction to improve engraftment efficiency, reduce surgical variability, and enable more scalable, minimally invasive treatment options. This review highlights the potential of biomaterial-assisted CECT as a next-generation regenerative strategy and outlines key challenges that must be overcome for successful clinical translation. Full article

Kidney transplantation is considered the best therapeutic option for patients affected by end-stage renal failure, but this possibility is limited by a shortage of donors. Living-donor kidney transplantation (LDKD) is a valuable option, frequently limited by immunological incompatibility between donor and recipient. This review will consider the possibility of performing living-donor kidney donation in the case of AB0 blood group incompatibility and the progress that has been made in this field. Kidney-paired donation is one possibility. This technique is the best option if there are numerous available pairs. This approach is possible because of national and international registries. The more diffuse technique is the desensitization of the recipients. Desensitization may be achieved in several ways, which are extensively discussed in this review. Recently, some published studies documented the possibility of enzymatically converting the A or B groups from the cells of the donor to the O group. This approach is only in a nascent stage but may represent the future, eventually associated with mild desensitization. Full article

The World Health Organization recommends the use of balanced energy protein (BEP) supplements during pregnancy in settings with a ≥ 20% prevalence of underweight women of reproductive age to reduce the risk of adverse health outcomes. Several countries are implementing BEP supplementation in varied formats. However, the implementation and monitoring of outcomes remain poor across countries. This qualitative study explores the experiences, opportunities, and challenges related to implementing national and sub-national BEP supplementation programs in nine countries (12 countries originally invited) to inform best practices. Methods: Semi-structured interviews were conducted with 15 personnel involved in its implementation in Haiti, India, Malawi, Mexico, Nigeria, Pakistan, Rwanda, Senegal, and Sri Lanka between October 2024 and March 2025. The interviewees in each country were predominantly implementation experts but also government officials involved in the provision of BEP supplementation. The transcripts were analyzed thematically, focusing on acceptability, adoption, appropriateness, cost, feasibility, and sustainability of outcomes. Results: In non-humanitarian settings (five countries), BEP supplementation was commonly integrated into the governmental health system or social protection programs. However, humanitarian contexts (four countries) often relied on partner-led (e.g., UN organizations) implementation. Clear operational protocols, including behavioral change communication strategies, facilitated the implementation. Community-based organization partnerships strengthened adherence; however, implementation costs, stock shortages, and geographic inequities in coverage varied and were limiting factors in scale-up, primarily in humanitarian contexts. Conclusion: In sum, two distinct implementation pathways emerged: government-led models characterized by policy integration, national ownership, and more stable systems, and humanitarian or donor-led models shaped by crisis response, external dependency, and non-committal challenges. Successful implementation of BEP supplements depends on the presence of effective policies, context-adapted design, integration into health systems, consistent funding, and effective monitoring. There is a need for implementation research to generate evidence on best practices when implementing BEP supplementation programs. Full article

Background/Objectives: Candidates with cardiometabolic risk are considered for living kidney donation more frequently because of the global organ shortage. The 2017 Kidney Disease: Improving Global Outcomes (KDIGO) guidelines introduced individualized risk assessment based on composite donor profiles rather than categorical exclusion, but the long-term implications of accepting donors with potential risk factors require careful evaluation. This review synthesizes current evidence on outcomes of living kidney donors with obesity, prediabetes, hypertension, and smoking. Methods: A literature search was conducted in PubMed/MEDLINE for studies published between 1 January 2000 and 28 February 2026, including cohort studies, registry analyses, meta-analyses, and clinical guidelines evaluating living kidney donors with obesity, smoking, prediabetes, or hypertension. Priority was given to large cohorts with long-term follow-up. Over 70 publications were included in the final synthesis. Findings were synthesized narratively by risk factors and outcomes. Results: Obesity was associated with an 86% increased end-stage kidney disease (ESKD) risk and 32% increased 20-year mortality. Central adiposity measures outperformed body mass index (BMI) for predicting estimated glomerular filtration rate (eGFR) decline. Post-donation weight gain increased the risk for developing hypertension and diabetes. Smoking conferred a 7.5-fold chronic kidney disease (CKD) risk, with impaired compensatory renal adaptation after donation. Prediabetic donors showed comparable outcomes to normoglycemic donors, with 57.8% reverting to normoglycemia at 10 years. Pre-donation hypertension increased 15-year ESKD risk 3-fold, but absolute risk remained low. At 15 years post-donation, over 50% of the donors developed hypertension. Glucagon-like peptide-1 (GLP-1) receptor agonists reduce diabetes progression by 73–94% in at-risk populations, but prospective studies in donors are lacking. Conclusions: Each risk factor carries quantifiable risks for individualized stratification. These risk factors usually coexist and interact. Refinement of risk prediction models, strategies for metabolic optimization and prospective evaluation of emerging pharmacologic therapies are key priorities. Full article

Liver transplantation remains the definitive treatment for end-stage liver disease and acute liver failure, yet a critical and persistent shortage of donor organs results in thousands of preventable deaths annually worldwide. Xenotransplantation has emerged as a potential solution to this structural deficit. This narrative review traces the evolution of liver xenotransplantation, from early non-human primate trials in the 1960s through the application of CRISPR/Cas9-driven multi-gene editing platforms in contemporary porcine donors. The immunological barriers that drove the transition from primate to porcine donors are examined, including hyperacute rejection mediated by anti-α-Gal antibodies, coagulation dysregulation and xenograft thrombotic microangiopathy. The genetic engineering strategies underlying current triple-knockout, ten-gene-edited donor pigs are reviewed alongside the preclinical non-human primate evidence establishing biological feasibility. The three pig-to-human liver xenotransplantation studies published between 2025 and 2026 are then analyzed, encompassing heterotopic auxiliary transplantation in a brain-dead decedent, extracorporeal liver cross-circulation and the first auxiliary liver xenotransplantation in a living recipient with a documented 171-day survival. These cases collectively provide preliminary evidence supporting proof-of-concept for porcine hepatic bridging therapy, with current evidence supporting a role for xenogeneic liver support as a temporary bridge to recovery or allotransplantation rather than definitive organ replacement. Xenograft thrombotic microangiopathy is identified as the principal remaining biological barrier, and the substantial translational challenges, including reproducibility, scalability and regulatory readiness that must be resolved before broader clinical application can be considered. Full article

Liver transplantation is the definitive therapy for end-stage liver disease, yet persistent organ shortages result in approximately 10% of recovered livers being discarded, with markedly higher discard rates among marginal grafts from elderly donors, donation after circulatory death (DCD), and those with macrovesicular steatosis. Machine perfusion (MP) has emerged as a paradigm-shifting preservation strategy with the potential to safely expand the usable donor pool. This narrative review examines the current evidence for three MP modalities—hypothermic machine perfusion (HMP), normothermic machine perfusion (NMP), and normothermic regional perfusion (NRP)—across various marginal donor populations, including elderly donors, steatotic grafts, donors with infectious diseases, and split liver transplantation. Current evidence demonstrates that MP significantly increases utilization of steatotic grafts with up to an eightfold rise in usage of severely steatotic organs. HMP consistently reduces non-anastomotic biliary strictures and early allograft dysfunction across donor types, while NMP enables real-time viability assessment and reduces post-reperfusion syndrome in steatotic grafts. NRP shows particular benefit in DCD organs, reducing biliary complications and improving one-year survival. Additionally, MP extends preservation times enabling next-day split liver transplantation and shows promise as a platform for ex situ antiviral therapy. Despite compelling evidence supporting MP in marginal grafts, widespread adoption remains constrained by high costs, logistical complexity, and the absence of standardized protocols. Future progress will require multicenter studies evaluating long-term outcomes alongside consensus-driven implementation frameworks. Full article

Cardiovascular diseases are a growing public health challenge in Ethiopia, worsened by limited access to diagnostics, including ECG, and shortages of specialized expertise. AI-powered ECG offers potential to improve diagnostic accuracy, efficiency, and access in resource-limited settings, but its adoption is influenced by policy, regulatory, financing, and governance factors, which are not well understood in Ethiopia. This study explored these system-level determinants using qualitative methods from September to October 2025 across federal institutions, four regions, and five tertiary hospitals. Twenty-five stakeholders, including policymakers, regulators, digital health experts, and hospital leaders, were interviewed. Data were transcribed verbatim, coded inductively, and analyzed thematically. Six themes emerged: policy and governance, regulatory frameworks, financing and cost considerations, data governance and bias, integration barriers, and sustainability recommendations. Findings showed AI-powered ECG interpretation aligns with Ethiopia’s digital health and noncommunicable disease priorities, but the country lacks AI-specific health policies, clear regulations, and dedicated budgets. Financing is largely donor-dependent, data governance and algorithmic bias remain concerns, and infrastructure gaps and digital skill shortages limit readiness. Study participants recommended learning from prior digital health projects, coordinated scale-up, phased implementation, and continuous monitoring. Effective adoption will require context-specific policies, sustainable financing, robust regulation, strong data governance, and careful system integration to ensure equitable, responsible, and sustainable use. Full article

Corneal fibrosis, clinically referred to as corneal scarring, disrupts the normal architecture and transparency of the cornea and remains a major cause of visual impairment worldwide. Although corneal transplantation can restore vision, its effectiveness is constrained by limited accessibility, donor tissue shortages, and the risk of allograft rejection. Treatments with human corneal stromal stem cells (hCSSCs) have demonstrated scarless healing in preclinical models of acute corneal injury. Here, we report that hCSSCs also modulated pre-existing corneal opacities. We established a reproducible in vivo model of chronic corneal opacity. Given that scar severity varies among corneas even after identical injuries, we developed a non-invasive, image-based method to quantify opacity volume longitudinally in individual corneas. Using this approach, we evaluated the scar-reducing potential of three hCSSC batches previously shown to inhibit acute scarring. Following cell treatment, the pre-existing opacity volumes gradually decreased. In vitro, hCSSCs exposed to pro-inflammatory stimulus exhibited increased metalloproteinase (MMP) activity relative to tissue inhibitor of metalloproteinase (TIMP), as indicated by an elevated MMP2/TIMP2 ratio. This shift may promote matrix remodeling and scar resolution. Overall, our findings provide proof-of-concept for hCSSC-based therapy as a strategy to reduce established corneal scarring and restore corneal transparency. Full article

Background: To address organ shortage and reduce waitlist mortality, the use of extended criteria donors (ECDs) in heart transplantation is increasing. Methods: We retrospectively analysed outcomes in 236 heart transplant recipients: 140 received standard donor (SD) hearts and 96 received ECD hearts. Results: No significant differences were found in early or mid-term survival between the SD and ECD groups with a 30-day mortality rates of 13% vs. 10% (p = 0.662) and estimated 1-year survival of 75% (95% CI: 62.3–78.3%) and 71% (95% CI: 55.3–76.2%) (p = 0.556), respectively. Mechanical ventilation prior to transplant (p < 0.001), ischemic time (p = 0.022), peripheral vascular disease (p = 0.011), and chronic obstructive pulmonary disease (p = 0.022) were the only independent predictors of mortality. Conclusions: In our cohort, heart transplantation using ECD was not associated with increased early or mid-term adverse events. This approach may help expand the donor pool without compromising post-transplant outcomes. Full article

End-stage liver disease caused by advanced fibrosis and cirrhosis remains a major global burden, yet its treatment is limited by donor organ shortages. Bioengineered liver scaffolds offer a promising alternative, but their efficacy is often limited by thrombosis, insufficient vascularization, and poor graft integration due to inadequate endothelialization. To overcome these challenges, we employed LXW7 αvβ3 integrin targeting peptide with high endothelial cell specificity and low platelet affinity to enhance re-endothelialization and hemocompatibility of decellularized liver scaffold (DLS) and thereby improve hepatic integration and function. LXW7 was covalently conjugated to the decellularized rat liver scaffold via EDC/NHS-mediated carbodiimide coupling and subsequently reseeded with human umbilical vein endothelial cells (HUVECs) and cultured in a perfusion bioreactor to promote endothelialization. LXW7 immobilization significantly improved HUVECs attachment and proliferation, achieving approximately 81% vascular coverage, while sustaining the endothelial function. Ex vivo blood perfusion showed minimal thrombus formation and markedly reduced platelet adhesion, demonstrating enhanced hemocompatibility. Following confirmation of endothelialization, scaffolds were recellularized with hepatocellular carcinoma (HepG2) cells and HUVECs. LXW7 modified scaffolds promote organized hepatocyte distribution, sustained albumin expression, and increased urea secretion. In vivo implantation of LXW7-DLS into the omentum of mice promoted robust host endothelial recruitment and enhanced neovascularization, highlighting the scaffold’s excellent biocompatibility and good integration with surrounding tissues. Moreover, in vivo implantation of LXW7 recellularized scaffolds into a thioacetamide-induced fibrotic mouse liver resulted in reduced collagen deposition and lowered serum ALT/AST levels, demonstrating hepatic regeneration and extracellular matrix remodeling. Overall, our results showed that LXW7-modified DLS promotes stable endothelialization, improves hemocompatibility, and enhances hepatic function, underscoring its translational potential for the development of vascularized transplantable liver grafts. Full article