Search Results (1,898)

(1) Background: Cerium silicate (CeSi) nanoparticles (NPs) have potential as a restorative filler particle with multifunctional properties to improve longevity. To increase the biological activity, these nanoparticles can be fabricated with ultrasmall pores (mesoporous) (MPCeSi-NP) that can be loaded with a polyphosphate inhibitor, such as gallein. (2) Methods: MPCeSi-NPs were custom-synthesized with a microemulsion method, using cetyltrimethylammonium bromide (CTAB) as a template for self-assembly. Biocompatibility with oral keratinocytes/fibroblasts was tested, with the addition of examining the biomineralization potential with human bone-marrow-derived mesenchymal stromal cells (BM-MSCs). MPCeSi-NP, loaded with gallein, was tested against Rothia dentocariosa (Rd). MPCeSi-NP was added to a resin matrix of triethylene glycol dimethacrylate (TEGDMA) and Bisphenol A-glycidyl methacrylate (BisGMA) with subsequent mechanical properties evaluation. (3) Results: MPCeSi-NPs had high biocompatibility with oral keratinocytes and fibroblasts, especially at concentrations below 300 µg/mL. MPCeSi-NPs induced the biomineralization of BM-MSCs. Higher cerium levels increased mineralization. MPCeSi-NP had weak antimicrobial activity against Rd. At 1% wt, MPCeSi-NPs did not reduce the polymerization potential and mechanical properties of a TEGDMA:BisGMA polymer material, with controlled release of gallein in a simulated degradation model. (4) Conclusions: MPCeSi-NPs are highly biocompatible and bioinductive and have the potential to improve the biological response of current restorative materials. Full article

Recurrent intrauterine adhesions (IUA) and refractory thin endometrium are associated with impaired endometrial regeneration, reduced implantation, and poor live birth outcomes. Regenerative therapy using mesenchymal stromal cells (MSCs) has shown promising results; however, factors associated with reproductive success remain unclear. In this prospective, single-centre, single-arm uncontrolled observational study, 35 women with recurrent IUA and thin endometrium (<7 mm) unresponsive to standard surgical and hormonal therapy received combined subendometrial and systemic administration of placenta-derived MSCs. The primary endpoint was live birth. Secondary endpoints included clinical pregnancy rate, time to pregnancy, endometrial thickness changes, uterine blood flow (resistance index, RI), and anti-Müllerian hormone (AMH) levels. Univariable logistic regression was performed to identify factors associated with live birth. Clinical pregnancy occurred in 13/35 patients (37.1%), and live birth was achieved in 11/35 (31.4%). Median time to pregnancy was 7 (5–8) months. Shorter duration of infertility or prior pregnancy loss (OR 1.55 per year; 95% CI 1.10–2.57), AFS stage I adhesions (OR 6.8; 95% CI 1.1–42; p = 0.04), lower baseline RI in uterine, arcuate and radial arteries, and higher baseline AMH (OR 2.59 per doubling; 95% CI 1.15–6.89) were significantly associated with live birth. Endometrial thickness increased after therapy but was not significantly associated with live birth. No severe adverse events were observed. Placenta-derived MSC therapy was followed by live birth in 31.4% of women with recurrent IUA and refractory thin endometrium. A shorter duration of reproductive disorders, less severe adhesions, lower baseline RI in uterine, arcuate and radial arteries, and higher AMH levels were associated with live birth after treatment and may help identify patients with a more favourable reproductive prognosis in future controlled studies. Full article

Introduction: platelet-rich fibrin (PRF) is a second-generation platelet concentrate which is known for promoting cell migration, tissue repair, angiogenesis and bone formation. In contrast, the specific effects of trauma-activated PRF on mesenchymal stromal cells (MSC) are not yet fully understood. The present study investigates systemic effects of surgical trauma-activated PRF on MSCs in vitro, analyzing their metabolic activity, inflammatory responses, and regenerative capacity to optimize advanced treatment concepts for severe fractures and injuries. Material & Methods: PRF membranes (T-PRF from trauma patients, C-PRF from healthy controls) were generated. After co-incubation with MSC cells for 24, 72, and 120 h, further investigations of metabolic activity (MTT assay) and gene expression analyses were performed. Results: for MTT assay, results especially showed a significantly higher metabolic activity of T-PRF after 120 h. ELISA-results measuring cytokine levels (CXCL10, IL-6, VEGF, and IDO) exposed a frequent peak in T-PRF group at 72 h, declining slightly at 120 h. In the gene expression analyses, T-PRF exerted a comparatively stronger stimulating effect on MAPK14 and VEGFA after 24 h, while a decrease in gene expression for MAPK8, MAPK14, and RUNX2 was observed over time. Conclusion: surgical trauma-activated PRF seems to be a powerful inducer of early inflammatory and stress responses in MSCs with preserved angiogenic but limited osteogenic signaling. Therefore, a targeted balance between inflammatory activation and sustainable regeneration, as well as optimized preparation and possible combination with immunomodulatory approaches, appear to be crucial for the therapeutic success of PRF-based strategies. Full article

Background: Gliomas are characterized by a high degree of molecular heterogeneity, which impairs the reproducibility of predictive biomarkers derived from bulk-based molecular profiling due to immune/stromal contamination of tumors and the high prevalence of the IDH mutation signature. Methods: In this study, we used MOFA+ to derive intrinsic molecular signatures from transcriptional, methylation, and genomic profiles of a cohort of 667 diffuse gliomas in the Cancer Genome Atlas database. Thereafter, factor scores were derived for two separate Chinese Glioma Genome Atlas batches (Batch 1, n = 325; Batch 2, n = 693) without any retraining on the model. The prognostic independence of identified molecular signatures was assessed using multivariable Cox regression adjusted for IDH mutation status and tumor purity; purity-residualized survival analyses; IDH-stratified Cox regression in each cohort; validation by concordance index against established molecular signatures; and survival extreme profiling. To characterize the biological significance of factor signatures, we projected gene set signatures corresponding to each factor signature onto a single-cell RNA-seq dataset of GBM (GSE131928). Results: MOFA+ identified 12 latent factors, of which a vascular–extracellular matrix (ECM) remodeling axis (Factor 1) explained the highest multi-omics variance (24.9%) and was the strongest independent prognostic factor. In multivariable Cox regression adjusting for IDH status and tumor purity, Factor 1 remained independently prognostic (HR = 1.67, 95% CI 1.27–2.20, p = 0.0002); in a fully-adjusted model additionally including age, WHO grade, MGMT methylation, and 1p/19q codeletion (plus radiotherapy and chemotherapy status in the CGGA cohorts), Factor 1 remained prognostic in both CGGA cohorts (CGGA1: HR = 1.50, p = 3.8 × 10⁻⁵; CGGA2: HR = 1.18, p = 0.003) but lost significance in TCGA (HR = 1.04, p = 0.83), consistent with the cohort-dependent magnitude reported in the IDH-stratified and meta-regression analyses below. Purity-residualized survival analysis showed negligible attenuation of the Factor 1 signal (raw HR = 3.57 vs. residualized HR = 3.72; concordance 96.5%). Within IDH-wildtype gliomas, Factor 1 was significant in both external validation cohorts (CGGA1: HR = 1.64, FDR = 4.6 × 10⁻⁶; CGGA2: HR = 1.20, FDR = 0.02), though the TCGA IDH-wildtype subgroup showed a trend that did not survive FDR correction (FDR = 0.060). All validation was performed without model retraining. Within IDH-mutant gliomas, Factor 1 was strongly prognostic in both CGGA cohorts but was not significant in TCGA (HR = 1.17, FDR = 0.33). These findings should therefore be interpreted as consistent in directionality across cohorts but not uniformly replicated at the FDR-adjusted significance threshold in the TCGA discovery dataset. Concordance index benchmarking on a matched subset (n = 503) showed Factor 1 achieved discrimination comparable to the Mesenchymal signature (C = 0.797 vs. 0.801; ΔC = −0.004) while outperforming four other established classifiers. Factor 1 consistently separated patients with extreme survival phenotypes (OS < 6 vs. >15 months) across all three cohorts (all log-rank p < 0.001). Projection onto a single-cell GBM atlas (GSE131928), supported by inferCNV-based malignant-cell classification, localized the Vascular–ECM program to malignant cells and the Immune–ECM axis to myeloid compartments. Conclusions: The Vascular–ECM axis is a consistent, prognostic program robust to purity adjustment for diffuse gliomas that remains relevant across IDH-defined subgroups in three independent datasets comprising 1685 patients. The Vascular–ECM axis is a reproducible, purity-robust prognostic program in diffuse glioma, with directionally consistent adverse effects across TCGA, CGGA Batch 1, and CGGA Batch 2 (pooled n = 1685). Given the strong co-loading of endothelial, ECM, and myeloid genes observed in the single-cell projection, Factor 1 is best interpreted as a vascular/ECM-associated tumor–microenvironment ecosystem program rather than a malignant-cell-autonomous signature. Its FDR-adjusted significance within IDH-stratified subgroups is cohort-dependent and robust in both CGGA cohorts but attenuated in the TCGA IDH-wildtype (FDR = 0.060) and TCGA IDH-mutant (FDR = 0.33) strata. The pooled signal should therefore be interpreted as evidence of a generalizable biological program rather than a uniformly replicated subgroup-specific biomarker. It is possible to calculate factor scores based on RNA sequencing alone using fixed loadings (Z = XWᵀ), which may have implications for future translational applications. All findings are correlative; a causal role for the Vascular–ECM program in glioma progression, invasion, or therapy resistance remains to be established through functional perturbation experiments. Full article

This scoping review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) guidelines. It summarizes advances in fibroblast activation protein inhibitor (FAPI) positron emission tomography (PET) for oncologic and fibroinflammatory diseases. FAP is expressed broadly on activated mesenchymal cells—including cancer-associated fibroblasts (CAFs) and myofibroblasts within desmoplastic tumor stroma, FAP-positive tumor cells in selected sarcomas, and activated fibroblasts in chronic fibroinflammatory disorders such as rheumatoid arthritis, Crohn’s disease, and organ fibrosis. By targeting these activated fibroblasts, [⁶⁸Ga]- and [¹⁸F]-labeled FAPI tracers provide high tumor-to-background contrast, particularly in desmoplastic and stromal-rich cancers. Compared with [¹⁸F]FDG, FAPI PET demonstrates superior lesion conspicuity in selected malignancies and enables a streamlined, non-fasting imaging workflow. Beyond oncology, FAPI PET is emerging as a promising tool for assessing cardiac fibrosis, pulmonary inflammation, and autoimmune conditions characterized by fibroblast activation. A systematic literature search of PubMed and Scopus was performed for peer-reviewed publications from 1 January 2018 to 28 February 2026. Inclusion criteria encompassed original studies, systematic reviews, meta-analyses, clinical guidelines, case series, and case reports reporting on FAPI-targeted PET in human subjects or translational models, published in English. After screening, 256 sources met the eligibility criteria and are included. The development of standardized SNMMI/EANM imaging protocols, along with ongoing multicenter trials and the first prospective phase 2 clinical trial of ⁶⁸Ga-FAPI-46 PET with histopathological confirmation, now supports the reproducible implementation of FAPI PET across institutions. FAPI PET demonstrates strong translational potential, largely due to its favorable biodistribution, safety profile, and theranostic flexibility. However, its widespread use in routine clinical practice is contingent upon large-scale clinical validation, structured reader training, and formal regulatory approval. In conclusion, FAPI PET represents a maturing molecular imaging platform targeting activated fibroblasts across oncologic and fibroinflammatory diseases. Its widespread adoption into clinical practice requires large-scale prospective trials, reader training, standardized reporting, and regulatory approval—all of which are now actively underway. Full article

Nickel (Ni) is a ubiquitous trace metal, yet its physiological dynamics and dose-dependent roles in skeletal biology remain unclear. Here we combined elemental mapping, cellular assays, multi-omics and mouse models to define how Ni availability modulates osteogenesis. Ni, together with Manganese (Mn), chromium (Cr) and copper (Cu), was readily detectable in serum from both mice and humans. In situ LA–ICP–MS further showed that Ni levels in embryonic calvaria rose significantly across stages and CaO exhibited a consistent upward trend, suggesting coordinated accumulation of Ni with cranial mineralization. In vitro, Ni exerted biphasic effects on bone marrow mesenchymal stromal cells (BMSCs): high-dose Ni (100 μM) suppressed proliferation, elevated ROS, and induced time-dependent upregulation of Hmox1 and Nos2, consistent with escalating oxidative/nitrosative stress. By contrast, low-dose Ni (0.1 μM) enhanced matrix mineralization, whereas this pro-mineralization effect was attenuated at higher concentrations. In vivo, both Ni deprivation and Ni overload impaired bone formation: a Ni-free diet caused trabecular rarefaction and reduced mineral apposition, while high Ni hindered bone development of mice, especially in the early-stage intake. Mechanistically, RNA-seq and Ni-NTA proteomics identified Ni-driven osteogenic transcriptional remodeling and increased Ni-binding proteins, prioritizing integrin-linked kinase (ILK) as a Ni-inducible binder. ILK was required for osteogenic differentiation, and low-dose Ni activated AKT–mTOR signaling in an ILK-dependent manner. Finally, low-dose Ni-pretreated collagen scaffolds enhanced calvarial defect repair. Together, these findings define a narrow physiological window in which Ni supports osteogenesis via ILK–AKT–mTOR, whereas both deficiency and excess disrupt skeletal accrual. Full article

Coronary artery bypass grafting (CABG) using the autologous saphenous vein (SV) remains widely performed for obstructive atherosclerosis; however, vein graft disease drives recurrent ischaemia through early thrombosis and progressive intimal hyperplasia, and accelerated atherosclerosis developing within the grafts. Extracellular vesicles (EVs) are membrane-bound particles that transfer proteins, lipids, and microRNAs between cells. They modulate endothelial dysfunction, vascular smooth muscle cell phenotypic switching, inflammation, and coagulation, which are core processes in vein graft remodelling. Arterialisation exposes the vein to abrupt rises in shear stress, cyclic stretch, and intraluminal pressure. These forces increase EV release and reshape EV cargo in experimental systems, suggesting a potential mechanism for amplifying early graft injury which warrants direct investigation in vein tissue. This review synthesises current evidence for cell-specific EV contributions from ECs, vascular smooth muscle cells, platelets, and macrophages, and appraises EV-associated microRNAs with biomarker potential relevant to graft failure pathways. We also review therapeutic strategies that may modulate EV signalling including antiplatelet therapy, statins, KCa3.1 inhibition, and pro-reparative mesenchymal stromal cell-derived EVs. No published clinical studies evaluate EV-based biomarkers specifically for saphenous vein graft patency, and none prospectively predict saphenous graft failure. CABG provides a well-defined time zero event that enables longitudinal sampling and risk stratification. Prospective studies linking EV phenotypes and miRNA signatures to imaging-defined graft outcomes are needed to support clinical translation. Full article

Background: Knee osteoarthritis (KOA) is a major cause of disability worldwide, and adipose-derived stromal vascular fraction (SVF) has emerged as a potential regenerative treatment to modify disease progression. Objective: This study aimed to assess the effectiveness of autologous adipose-derived stromal vascular fraction (SVF) through intra-articular injection to treat early-stage knee osteoarthritis (KOA). Materials and Methods: This multicenter observational study (2019–2023) included adults aged 18–65 years with radiographically confirmed knee osteoarthritis. Patients were assigned to one of two groups through a retrospective, non-randomized process based on the actual treatment received during their clinical follow-up. Group T received intra-articular adipose-derived stromal vascular fraction (SVF) injections, while Group C received conservative treatment with non-steroidal anti-inflammatory drugs (NSAIDs) only. SVF was obtained from abdominal adipose tissue using a standardized closed-system device and injected intra-articularly. Pain and functional outcomes were assessed using the Visual Analog Scale (VAS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) at baseline and at 1, 3, 6, 9, and 12 months. Results: Sixty-seven patients (41 SVF, 26 controls) were included, with comparable baseline characteristics (all p > 0.05). Preoperative VAS was lower in the SVF group (7.44 ± 1.44 vs. 8.31 ± 1.09; p = 0.029). At 12 months, VAS significantly decreased to 3.77 ± 1.49 in the SVF group, whereas it increased to 8.85 ± 0.67 in controls (p < 0.001). Similarly, baseline WOMAC scores were lower in the SVF group (62.6 ± 21.7 vs. 76.8 ± 8.76; p = 0.004). At 12 months, WOMAC improved to 29.4 ± 15 in the SVF group but worsened to 87.6 ± 3.21 in controls (p < 0.001). Within-group improvements were significant only in the SVF group (p < 0.001). No procedure-related complications were observed. Conclusions: The autologous adipose-derived stromal vascular fraction is an effective treatment option for early-stage KOA patients. However, a prospective, randomized, controlled study is warranted. Full article

Mesenchymal stromal cells (MSCs) are multipotent cells characterized by their regenerative capacity and strong immunomodulatory properties. In recent years, MSC-based therapy has attracted significant attention as a potential treatment for a wide range of immune-mediated and degenerative diseases. The therapeutic effects of MSCs are primarily mediated through paracrine signaling and secretion of cytokines that regulate immune responses and promote tissue repair. This review focuses on five key cytokines involved in MSC immunomodulation: interleukin-6 (IL-6), interleukin-10 (IL-10), transforming growth factor-beta (TGF-β), tumor necrosis factor-alpha (TNF-α), and interleukin-1 beta (IL-1β). These cytokines interact within a complex signaling network that allows MSCs to suppress excessive inflammation and restore immune balance. The role of MSC therapy is examined in several clinically relevant conditions, including systemic lupus erythematosus, systemic sclerosis, ischemic stroke, spinal cord injury, diabetes mellitus, and female infertility. Across these diseases, MSCs demonstrate the ability to inhibit pro-inflammatory immune cell activity, promote regulatory immune phenotypes, reduce oxidative stress, and stimulate regeneration through the secretion of growth factors and extracellular vesicles. Despite promising experimental and early clinical findings, several limitations remain, including variability in MSC sources, limited cell survival after transplantation, and the need for optimized dosing strategies. Overall, MSC therapy represents a multifunctional therapeutic approach combining immunomodulation, anti-inflammatory activity, and regenerative support. Further research is required to better understand cytokine interactions, improve standardization of MSC-based treatments, and enhance clinical efficacy across diverse pathological conditions. Full article

Mesenchymal stromal/stem cells (MSCs) are increasingly investigated as intra-articular therapies for equine osteoarthritis (OA), although most studies have focused on allogeneic or combination-based approaches. Evidence supporting the use of autologous MSCs as a stand-alone treatment remains limited. The present study evaluated the safety and clinical evolution following intra-articular administration of autologous muscle-derived MSCs (mdMSCs) in horses with naturally occurring chronic OA. Thirteen horses with confirmed clinical disease were included. Each affected joint received a single injection, with the administered cell dose adapted to joint size (1 × 10⁷ or 2 × 10⁷ cells). Clinical assessments were conducted at baseline and at 6 and 12 weeks post-treatment using the American Association of Equine Practitioners (AAEP) lameness scale, together with a joint inflammation score and a composite total clinical score (TCS). Clinical scores decreased over time, with statistically significant improvements observed at both follow-up time points. Seven of thirteen horses met the predefined responder criteria based on AAEP improvement, including complete resolution of lameness in several cases. The treatment was well tolerated, with only mild and transient local reactions that resolved without intervention. These results indicate that intra-articular administration of autologous mdMSCs is associated with clinically relevant improvement in horses with chronic OA. Full article

Background/Objectives: Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic condition characterized by pelvic pain, urinary symptoms, and reduced quality of life, with limited effective treatment options. Regenerative approaches using adipose-derived mesenchymal stromal cells (MSCs) have shown promising preclinical results. This study aimed to evaluate the feasibility, safety, and preliminary efficacy of transurethral implantation of autologous micronized adipose tissue (MAT) in patients with refractory IC/BPS. Methods: We conducted a single-center retrospective observational pilot study including 20 patients with refractory IC/BPS treated between April and October 2024. Adipose tissue was harvested via liposuction and mechanically processed using a closed system (Matrigen device) to obtain minimally manipulated micronized adipose tissue. The product was injected transurethrally into the bladder submucosa. Patients were evaluated at baseline and at 1, 3, and 6 months using validated questionnaires (ICSI/ICPI, SF-36, MOS Sexual Function), verbal rating scale (VRS) for pain and urgency, urodynamic parameters, and cystoscopic findings. Changes over time were assessed using paired non-parametric tests. Results: At 6 months, 65% of patients met responder criteria, defined as ≥50% improvement in pain and/or urgency or a positive global response. Significant improvements were observed in IC Problem Index, SF-36, MOS scores, and VRS urgency, while VRS pain improved significantly at 6 months. Urodynamic parameters showed increased bladder capacity (median 275 to 325 mL, p < 0.001) and reduced post-void residual volume (80 to 40 mL, p < 0.001). Cystoscopic findings demonstrated improvement in bladder mucosal appearance. The procedure was well tolerated, with no serious adverse events or immunological complications observed. Conclusions: In this exploratory pilot study, transurethral implantation of autologous micronized adipose tissue was associated with improvements in symptoms, bladder function, and cystoscopic findings in patients with refractory IC/BPS. These results support the feasibility and potential role of minimally manipulated adipose-derived therapies in this setting. Given the small sample size and absence of a control group, findings should be considered exploratory. Larger controlled studies are warranted to confirm efficacy and evaluate long-term outcomes. Full article

Background/Objectives: An ideal bone scaffold should promote bone cell growth and functional vascularization, hence the importance of imbuing biomaterials with pro-angiogenic cues. In this work, silica-based bioactive glasses, either pristine (SBA3) or doped with copper (SBA3_Cu), were embedded in poly(ε-caprolactone) (PCL), which was also used as a control. Methods: In vitro co-cultures of adipose-derived mesenchymal stem/stromal cells (ASCs) and human microvascular endothelial cells (HMEC-1s) were kept in α-MEM, MCDB131, and EndoGRO media to test the biomaterials. The co-cultures were visualized by immunofluorescence and SEM, while flow cytometry was performed to characterize cellular immunophenotype. The angiogenic potential was evaluated using conditioned media of co-cultures to perform a tubulogenesis assay and VEGF-A quantification. Results: Immunophenotypic analysis showed a significant decrease in the endothelial CD31+ cellular subset, whereas the OB-like cellular subset expressing CD105, CD73, CD90, and ALP increased in all culture media over time. In α-MEM, HMEC-1s were unable to form a capillary network independent of the substrates. A more organized network was visible when co-cultures were plated on PCL, in MCDB131 and EndoGRO, or if they were kept in EndoGRO on PCL/SBA3_Cu. The VEGF-A concentrations were similar in the conditioned media from co-cultures grown on PCL/SBA_Cu, in EndoGRO, and on PCL and PCL/SBA3, in MCDB131. Conclusions: The presence of copper did not promote the angiogenic potential of HMEC-1, likely due to the low concentration of released copper ions and the predominant osteoinductive effect of the other ions released by the bioglass. A re-evaluation of formulation and structure of bioglass scaffold could enhance the angiogenic potential. Full article

Cardiovascular diseases remain the leading cause of mortality in developed countries. Among these conditions, acute myocardial infarction (AMI) is associated with particularly high rates of cardiac morbidity and mortality. Cardiac development in mammals is primarily dependent on cardiomyocyte (CM) proliferation during embryonic and early postnatal stages. However, following birth, the proliferative capacity of CMs declines markedly, with only limited cellular renewal occurring during adult life in response to pathological injury. Consequently, the irreversible loss of functional cardiomyocytes and the subsequent formation of fibrotic scar tissue frequently lead to persistent cardiac dysfunction and progressive impairment of cardiac physiology. Cardiomyocyte self-renewal is a tightly regulated process involving multiple molecular pathways. Among factors implicated in this regulation, microRNAs (miRNAs) have emerged as key modulators coordinating both cardiac development and tissue repair mechanisms. In this context, extracellular vesicles (EVs) have attracted considerable interest as potential modulators of these regenerative processes. In particular, mesenchymal stromal cells (MSCs) represent a promising therapeutic platform due to their immunomodulatory and anti-fibrotic properties demonstrated across multiple in vitro and in vivo models. Furthermore, the therapeutic potential of MSC-derived EVs can be enhanced through bioengineering approaches aimed at improving targeted molecular delivery. In this review, we summarize recent advances in the development and application of EV-based therapeutic strategies, with particular emphasis on their potential use as advanced therapy medicinal products (ATMPs) for cardiovascular regeneration and repair. Full article

Mesenchymal stem/stromal cells (MSCs) are multipotent progenitor cells with potent immunomodulatory properties, making them attractive candidates for treating inflammatory and autoimmune diseases. A key mediator of MSC-induced immunosuppression is programmed death-ligand 1 (PD-L1), a checkpoint molecule that interacts with PD-1 on immune cells to regulate immune responses and promote tolerance. This review synthesizes current evidence on the role of PD-L1 expression in MSCs, emphasizing its effects on both the innate and adaptive immune systems, its therapeutic potential, and its utility as a biomarker for MSC potency and clinical efficacy. We examine how PD-L1 modulates T cell activation, dendritic cell maturation, macrophage polarization, and cytokine profiles, including its role in exosomal contexts. Additionally, we highlight its synergistic interactions with other immune checkpoints and discuss its dual function as both a therapeutic effector and a dynamic biomarker. Finally, we explore its relevance in clinical contexts such as autoimmune diseases, graft-versus-host disease, sepsis, and transplantation and conclude with a discussion of challenges and future directions in harnessing PD-L1 for MSC-based therapies. Full article

Mesenchymal stromal cells (MSCs), also known as multipotent stromal cells or mesenchymal stromal cells, support cell growth and viability through the secretion of trophic factors and immunomodulatory molecules. Their secretome exerts cytoprotective effects in the brain, although the mechanisms underlying MSC-mediated neurological recovery remain poorly understood. A substantial portion of the MSC secretome is delivered via extracellular vesicles (EVs), membrane-bound particles that facilitate intercellular communication. EVs derived from MSCs of various origins exhibit therapeutic potential, and numerous studies are examining the miRNA and protein cargo contained within MSC-EVs. Despite these efforts, methodological differences across the literature and the inherent variability associated with MSC sources have limited data interpretation and identification of EV-factors which may be responsible for neuroprotection. In this study, we have reviewed proteomic, transcriptomic and lipidomic datasets from a selection of recent MSC-EV studies, to identify shared cargo components that may contribute to promoting cell repair and plasticity in brain, counteracting neurodegeneration. Full article