ObjectiveTo systematically review and quantitatively synthesize in vivo evidence on extracellular vesicle (EV)-based therapies for regenerative endodontic procedures, focusing on mineralization and angiogenesis outcomes.MethodsWe conducted a systematic review and meta-analysis of in vivo preclinical dentoalveolar/regenerative endodontic models comparing EV-based interventions (exosomes/microvesicles/apoptotic bodies), alone or with scaffolds, versus control conditions. Searches were performed in Web of Science Core Collection and Scopus from inception to 31 December 2025, with reference screening. Random-effects meta-analyses pooled standardized mean differences (SMDs) for mineralization and angiogenesis; heterogeneity was assessed using I2. Risk of bias was evaluated using the Systematic Review Centre for Laboratory animal Experimentation tool.ResultsTwenty-one studies met inclusion criteria; seven were included in the mineralization meta-analysis and five in the angiogenesis meta-analysis. EV-based therapies significantly increased mineralization versus controls (SMD = 6.43; 95% confidence interval (CI) [3.13-9.73]; I2 = 91%) and angiogenesis (SMD = 7.89; 95% CI [3.94-11.85]; I2 = 82%). Subgroup analyses suggested stronger effects for EVs derived from dental pulp stem cells, stem cells from human exfoliated deciduous teeth, and stem cells from apical papilla. Risk of bias was predominantly unclear due to limited reporting of randomization and blinding. Considerable heterogeneity, small numbers of pooled studies, and variability in EV isolation, characterization, dosing, and outcome assessment limit generalizability and translation.ConclusionsEV-based therapies enhance mineralization and angiogenesis in preclinical regenerative endodontic models, with dental stem cell-derived EVs showing the greatest apparent potential. However, effect sizes should be interpreted cautiously given very high heterogeneity and methodological/reporting limitations.PROSPERO registration: Centre for Reviews and Dissemination 420251107328.

Diagnostic evaluation and management of nontraumatic osteonecrosis of the femoral head (ONFH) vary substantially. This systematic review was conducted to inform development of the Association Research Circulation Osseous (ARCO) clinical practice guideline for diagnosis and treatment of ARCO stages I to III ONFH.

Significant progress has been made in research on chronic pancreatitis (CP). It is essential to analyze recent trends in this field to guide future clinical investigations.

Diabetic foot ulcers (DFUs) represent a debilitating complication of diabetes characterized by high rates of morbidity and mortality, yet conventional management often yields limited efficacy. Although cell-based therapies offer a promising therapeutic avenue, their clinical efficacy and optimal target populations remain to be definitively established.

The objective of the study is to systematically evaluate the efficacy and mechanisms of action of stem cell-derived exosomes from various sources (including adipose tissue [AD-MSCs] and bone marrow [BM-MSCs]) in treating diabetic foot ulcers (DFUs) based on preclinical evidence.

Knee osteoarthritis (KOA) remains a leading cause of disability, and mesenchymal stem cells (MSCs) show potential for KOA treatment. However, existing studies demonstrate conflicting results on the optimal dose and tissue source of MSCs for KOA treatment. This gap limits evidence-based treatment decisions.

Exosome therapy represents an emerging regenerative medicine approach for optimizing wound healing and reducing scarring. Extensive pre-clinical research on human placental mesenchymal stem cell-derived exosomes (hpMSC-exosomes) demonstrates significant therapeutic potential in aesthetic and reconstructive surgery applications. Despite compelling preclinical evidence supporting the efficacy of exosomes in wound healing, human clinical studies remain scarce. The author's current study includes 738 patients treated with hpMSC-exosomes over a 7-year period across multiple aesthetic and reconstructive indications, with 175 cases involving wound healing and 118 cases involving scar therapy. The objective of this systematic review and meta-analysis is to comprehensively evaluate the current evidence for hpMSC-exosomes in wound healing and scar therapy, analyzing their mechanisms of action, clinical applications, and safety profiles through a review of preclinical studies, safety data, and clinical case series in both animals and humans. Analysis of the author's series will be included. Information sources included PubMed, Cochrane Library, EMBASE, Web of Science, and ClinicalTrials.gov resulting in a meta-analysis of 21 global preclinical studies (323 animals) which demonstrated superior outcomes compared with controls across multiple parameters: wound healing rate, neovascular density, re-epithelialization rate, and collagen deposition. hpMSC-exosomes demonstrated accelerated wound healing through enhanced angiogenesis, reduced inflammation, improved collagen production, and immunomodulatory effects. Most studies utilized rodent models, with limited translation to human trials. Current human evidence is predominantly based on early-phase trials, case series, and observational studies. Large-scale, well-designed clinical trials are essential to advancing exosome therapy in wound healing and scar management. hp-MSC-exosomes represent a promising therapeutic modality for wound healing and scar therapy with demonstrated safety and efficacy. Standardization of manufacturing processes and FDA approval remain critical for widespread clinical implementation. Level of Evidence: 3 (Therapeutic).

BackgroundIn recent years, research on mesenchymal stem cells (MSCs) for treating Discogenic Low Back Pain (DLBP) has been steadily increasing, yet there remains a lack of Meta-analysis focusing specifically on autologous MSCs (AMSCs) for this condition. This study comprehensively analyzes all published research on AMSCs in the treatment of DLBP and summarizes the evidence-based medical findings regarding the efficacy of this regenerative therapy for DLBP.MethodsA comprehensive literature search was conducted across PubMed, Embase, Web of Science, and Ovid databases for articles published from database inception through April 2025. Following rigorous screening of all identified studies investigating AMSCs for DLBP treatment and performing a meta-analysis to evaluate the collective evidence.ResultsFour studies were included in our analysis, all of which were prospective single-arm trials (PSATs). The meta-analysis demonstrated significant reductions in Visual Analog Scale (VAS) and Oswestry Disability Index (ODI). Pain score decreased by >30% and >50% from baseline, with incidence rates of 52.20%, 66.00%, 67.90%, and 76.80% for >30% reduction, and 34.21%, 50.74%, 69.32%, and 67.74% for >50% reduction at these respective time points. Subgroup analysis revealed no statistically significant difference in the incidence of >30% or >50% pain score reduction between the AMSCs + hyaluronic acid (HA) combination group and AMSCs monotherapy group at equivalent follow-up intervals.ConclusionIntradiscal injection of AMSCs demonstrates both safety and clinical efficacy in the treatment of DLBP. The 6-month follow-up represents a clinically meaningful timepoint for evaluating the therapeutic effects of AMSCs. No significant differences were observed between AMSCs combined with HA and AMSCs monotherapy in terms of clinical outcomes.

A multitude of studies have investigated the identification of unique antigens and genetic traits associated with cardiac stem cells (CSCs) since their discovery. This meta-analysis aims to assess the safety and efficacy of cardiac stem cells (CSCs), elucidate existing knowledge regarding their potential applications, and compare them with other novel therapeutic strategies for cardiac repair, including bone marrow cells (BMCs) and mesenchymal stem cells (MSCs). Researchers conducted a search of important indexing databases, including PubMed, Scopus, Cochrane Central, Web of Science (WOS), CINAHL, and Embase, to identify pertinent papers published from 1980 to January 2025. A total of 74 studies involving 5,420 participants were selected from 459 evaluated for the study. A total of 2,931 participants were allocated to the intervention group, whereas 2,489 were assigned to the placebo or control groups. The research encompassed 49 papers on BMC therapy, 17 on MSC therapy, five on CSC therapy, and three on ADRC therapy. A 0.4% enhancement in left ventricular ejection fraction (LVEF) [95% confidence interval (95% CI): 0.23-0.57; I2: 85%, P < 0.00001] was noted after stem cell therapy and in the stem cell therapy cohort, left ventricular end-systolic volume (LVESV) diminished by -0.33 mL (95% CI: -0.47 to -0.19; I2: 73%, P < 0.00001), whereas left ventricular end-diastolic volume (LVEDV) reduced by -0.18 mL (95% CI: -0.31 to -0.05; I2: 68%, P = 0.006). Furthermore, in this cohort, the six-minute walk test (6MWT) exhibited an increase of 0.2% (95% CI: 0.06-0.34; I2: 0%, P = 0.005), whereas the standardized mean difference of infarct size (IS) demonstrated a reduction of -0.36% (95% CI: -0.60 to -0.12; I2: 68%; P = 0.004). These findings augment the existing evidence and underscore the transformative potential of stem cell therapy in cardiac treatment.

Treatment with umbilical cord blood (UCB) for cerebral palsy (CP) remains promising but experimental and unproven. An updated meta-analysis is needed to assess the efficacy of UCB mononuclear cells (MNCs) in comparison to UCB-derived mesenchymal stromal cells (MSCs) to clarify future directions in the use of UCB to treat CP. An updated systematic review of published controlled clinical trials to November 2024 was conducted and identified ten trials (621 patients; 71% of all patients from 7 trials received UCB-MNCs). Three trials administered UCB-MSCs (30%) and one study compared UCB-MNCs to UCB-MSCs. In one study, MNCs were administered with or without erythropoietin. Eight studies (80%) administered allogeneic cells. Dosage and route of cell administration varied. Clinical outcome reporting was variable, but allowed for meta-analysis of change in GMFM motor scores at 12 months (included 9 groups across 7 studies). Using a random effects model, the standardized mean difference in GMFM scores between baseline and 12 months was higher in the intervention group compared to controls (M= 0.5828, 95% CI=[0.19,0.98], P-value= 0.004). Subgroup analysis using a random-effects model revealed no statistically significant difference in GMFM scores from baseline to 12 months compared to controls in the MNC group (MA = 0.3225, 95% CI = [-0.19, 0.84], P -value= 0.22), whereas in the MSC group, GMFM scores improved more significantly compared to controls (MB = 0.9192, 95% CI = [0.33,1.50], P-value = 0.002). In conclusion, infusion of UCB-MSCs appears promising, with improved GMFM scores at 12 months for patients with cerebral palsy. Larger randomized controlled trials that examine MSCs derived from cord blood and other tissues appears worthwhile. Longer follow-up addressing the breadth of relevant clinical outcomes in CP are needed to confirm potential benefits for patients with CP.

Tissue-engineering strategies combining mesenchymal stem cells (MSCs) or extracellular vesicles (EVs) with bone-regenerative scaffolds may improve healing of critical-size bone defects, yet their comparative efficacy remains unclear. We systematically searched PubMed, Embase, Scopus, Web of Science, and ProQuest for animal studies published up to July 1, 2025. Risk of bias was assessed using the SYRCLE tool. New bone formation was synthesized as bone volume/total volume (BV/TV) using conventional meta-analysis and Bayesian network fixed/random-effects models, reported as standardized mean difference (SMD) with 95% confidence interval (CI)/credible interval (CrI). Subgroup analyses were conducted by MSC source, EV use, scaffold type, anatomical site, and follow-up duration, with sensitivity analyses and assessment of publication bias. In total, 207 studies across 7 animal models were included. MSC-loaded scaffolds significantly enhanced bone regeneration compared with no treatment or scaffold alone, showing a strong short-term effect and consistent benefits at medium and long follow-up. Bone marrow MSC (BMSC)-laden scaffolds underperformed adipose-derived MSC (ADSC)-laden scaffolds, and BMSC-derived EVs further improved outcomes compared with cell-free scaffolds. Calvarial defect models demonstrated greater gains than long-bone models. Network meta-analysis suggested multi-component composite scaffolds had the highest potential for new bone formation among cell-free designs. Overall, MSCs/EVs combined with supportive scaffolds markedly increase bone regeneration in preclinical models, but heterogeneity in models, biomaterials, dosing, and outcome reporting limits direct clinical translation, underscoring the need for standardized protocols and core outcome sets. STATEMENT OF SIGNIFICANCE: This comprehensive meta-analysis incorporated network comparisons across diverse mesenchymal stem cells (MSCs) or extracellular vesicles (EVs) sources and biomaterial categories. It reveals that MSC-EVs, particularly when combined with scaffolds or hydrogels, are the most effective in improving BV/TV ratio (bone volume/total volume) and histological outcomes in animal bone defect models. These data indicate that MSC or EV-enhanced biomaterial strategies may be leading candidates for repairing critical-sized defects and provide a standardized roadmap for transitioning preclinical success into clinical practice.

Stroke is one of the most common causes of death and permanent neurological disabilities worldwide yet neuroprotective or regenerative therapies do not exist. Genetically modified neural stem cells (NSC) could help overcome key limitations of naïve or unmodified NSCs and improve therapeutic efficacy. The aim of this systematic review and meta-analysis is to evaluate existing preclinical literature using animal models to compare the therapeutic effects of genetically modified NSCs for stroke compared to naïve NSCs or vehicle control.

To support the development of a national guideline on stem cell therapy, the Department of Health Research, India, commissioned this systematic review to evaluate the efficacy and safety of various stem cell types in patients with type 1 and type 2 diabetes mellitus (DM), focusing on patient-important outcomes.

MSCs are an important component of the TME and play a key role in tumor progression. Based on existing in vitro studies, this research aims to investigate the role of mesenchymal stem cells in the EMT of HNSCC and its related mechanisms.

Acute lymphoblastic leukemia (ALL) is a hematologic malignancy characterized by malignant transformation of lymphoid precursor cells. ALL prognosis differs considerably, especially between pediatric patients and adult patients, with poor response to therapy in adults. MicroRNAs (miRNAs), small non-coding RNAs that regulate the expression of genes, are possible cancer biomarkers that predict cancer prognosis. This systematic review and meta-analysis evaluates miRNAs as prognostic biomarkers in ALL and extends the findings through ceRNA network and single-cell RNA seq analyses of validated target genes.

This meta-analysis comprehensively evaluates the therapeutic efficacy and mechanisms of mesenchymal stem cells (MSCs) and their exosomes in rodent models of hepatic ischemia-reperfusion injury (HIRI), providing preclinical support for future clinical translation.

Background/Objectives: Stemness has been proposed as a unifying driver of invasion, treatment resistance, and relapse in oral squamous cell carcinoma (OSCC). We synthesized two complementary evidence streams to determine whether higher stemness predicts poorer survival in OSCC: (i) computational stemness signatures derived from transcriptomic/epigenetic data and (ii) tissue cancer stem cell (CSC) immunophenotypes by immunohistochemistry (IHC). Methods: Following PRISMA 2020, we searched PubMed/MEDLINE, Embase, Scopus, and SciELO. Adults with histologically confirmed OSCC were eligible. Primary outcome was overall survival (OS); disease-specific survival (DSS) and recurrence-free survival (RFS) were secondary. Two parallel meta-analyses pooled effects within domains; random-effects restricted maximum likelihood (REML) models were applied. Results: Of 785 records, 11 studies met criteria. For computational signatures (k = 6), higher stemness was associated with poorer OS (pooled HR 2.24, 95% CI 1.61-3.12; I2 ≈ 49%). Sensitivity excluding the single unadjusted Kaplan-Meier (KM)-derived estimate yielded a similar effect (HR 2.13, 95% CI 1.56-2.89). For CSC-IHC (main analysis, k = 2), CSC-positive profiles predicted worse OS (pooled HR 2.01, 95% CI 1.42-2.84; I2 ≈ 0%); results were robust to excluding an internally inconsistent study (single-study HR 2.078). An exploratory sensitivity analysis, including a 1-year HR (different time horizon), increased heterogeneity and was not considered definitive. A functional meta-synthesis converged on epithelial-mesenchymal transition/extracellular matrix remodeling, hypoxia/glycolysis, redox/ferroptosis resistance, and ribosome/rRNA biogenesis, supporting biological plausibility across modalities. Conclusions: Across computational and IHC evidence, stemness consistently portends inferior OS in OSCC, offering a biologically anchored framework for risk stratification and testable therapeutic hypotheses.

Dioxins, are highly potent environmental carcinogens. Their toxic effects are mediated primarily by the Aryl Hydrocarbon Receptor (AhR). A comprehensive understanding of how AhR-induced genetic and epigenetic alterations drive carcinogenesis, especially through effects on cancer stem cells (CSCs), epithelial-mesenchymal transition (EMT) and transgenerational inheritance, remains imperative.

Peripheral neuropathies are common neurological disorders affecting sensory, autonomic, and motor nerves, with an estimated prevalence exceeding 2% in the general population. Typical symptoms include numbness and distal limb muscle weakness, resulting from somatosensory nerve damage. Here, we investigate the genetic architecture of mono- and polyneuropathies and their relationships with comorbid traits using data from FinnGen and the UK Biobank. Our genome-wide association study (GWAS) and meta-analysis identified 48 genome-wide significant (P < 5 × 10-8) independent loci and 66 fine-mapped credible sets. These included associations with genes involved in neurotransmitter signaling (HTR3A), immune function (HLA-DQB1, BCL11A), extracellular matrix remodeling (COL11A1, ADAMTS17, LOXL4), axon guidance and neural development (DCC, ETV1, NEGR1), and carpal tunnel syndrome (DIRC3). Public variant association data across cohorts, genetic correlation, and Mendelian randomization analyses supported shared genetic links of neuropathies with sleep problems, chronic pain, and psychiatric disorders. Together, our results highlight a strong polygenic basis for neuropathies and further confirm their genetic comorbid relationships with sleep, pain, psychiatric, and autoimmune traits.

Autologous fat grafting is a cornerstone in plastic and reconstructive surgery, yet its efficacy remains limited by variable resorption rates. Stromal vascular fraction (SVF) has emerged as a promising adjunct to enhance graft survival. This systematic review and meta-analysis aimed to evaluate the efficacy and safety of SVF-enriched fat grafting compared with conventional fat grafting techniques.