Lipedema is a chronic disorder that affects the subcutaneous adipose tissue of the lower and upper limbs and results in painful fat accumulations. During the reproductive life span, about 11% of women are affected; however, there are a high number of suspected undiagnosed and thus untreated cases.

This study aimed to evaluate the efficacy and safety of mesenchymal stem cell (MSC) therapy for osteoarthritis (OA) through a systematic review and meta-analysis of randomized controlled trials (RCTs), focusing on patient-reported pain and functional outcomes.

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.

Cancer stem cells (CSCs) are increasingly recognised as pivotal drivers of tumour recurrence and treatment resistance across multiple malignancies. Despite extensive preclinical investigations, the mechanisms by which CSCs mediate relapse after therapy remain insufficiently integrated and poorly translated into clinical frameworks.

Mesenchymal stem cells (MSCs) have shown promise in preclinical models for enhancing bone regeneration around dental implants. However, clinical evidence regarding their efficacy in maxillary sinus augmentation procedures for dental implants remains inconclusive.

Adipose-derived stem cell (ADSC)-enhanced fat grafting, including enrichment with stromal vascular fraction (SVF) and adipose-derived regenerative cells (ADRCs), has been increasingly used to improve fat graft survival and regenerative outcomes in reconstructive and aesthetic plastic surgery, yet long-term safety, efficacy, and mechanistic understanding remain variably reported. This systematic review aimed to evaluate real-world clinical evidence on the long-term safety, volume retention, and functional outcomes of ADSC-, SVF-, and ADRC-enriched fat grafting across aesthetic and reconstructive indications. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines, comprehensive searches of PubMed, Scopus, Web of Science, and the Cochrane Library identified 3158 studies, of which 12 met the inclusion criteria, encompassing randomized controlled trials and prospective non-randomized clinical studies assessing ADSC-, SVF-, or ADRC-assisted fat grafting with reported outcomes related to graft survival, clinical function, aesthetic performance, or safety. Across studies, ADSC and SVF enrichment generally improved volume retention compared with conventional fat grafting, with several randomized trials demonstrating graft survival rates of 60-80% at three to six months, and ADSC-assisted grafts consistently enhanced dermal regeneration by improving collagen organization, skin texture, and elastic fiber architecture. In reconstructive applications, SVF therapy reduced digital ulcers and pain in patients with systemic sclerosis, while ADRC-assisted grafting alleviated symptoms of breast cancer-related lymphedema despite limited objective limb-volume reduction, and patient satisfaction was high across all enrichment techniques. Safety outcomes were favorable, with no increase in infection, cyst formation, fat necrosis, or oncologic recurrence across follow-up periods of up to four years. Overall, ADSC-, SVF-, and ADRC-enriched fat grafting appear to offer meaningful improvements in graft survival, skin quality, and functional recovery with a strong safety profile across diverse clinical indications, although methodological heterogeneity and limited long-term data support the need for standardized, regulated, and mechanistically informed clinical protocols, as well as larger, long-term randomized trials to optimize techniques and guide clinical use.

The musculoskeletal system consists of bones, joint cartilage, tendons, ligaments, muscles, and their associated nerves and blood vessels. These components work together to maintain human movement and mechanical stability, serving as the critical foundation for sustaining life activities. In recent years, with the acceleration of population aging, the incidence of musculoskeletal-related diseases such as sarcopenia, muscle atrophy, osteoporosis (OP), osteoarthritis (OA), and tendon injuries has continued to rise, significantly impacting patients' quality of life and imposing a heavy social health burden. Mesenchymal stem cells (MSCs) have garnered widespread attention in tissue repair and regenerative medicine due to their excellent self-renewal capacity, multipotent differentiation potential, and low immunogenicity. Numerous studies have shown that the therapeutic effects of MSCs primarily depend on their paracrine actions, particularly the extracellular vesicles (EVs) they secrete, which play a crucial role in regulating tissue homeostasis and repairing damage. MSC-derived EVs possess biological functions similar to those of their parent cells and lack immunogenicity and tumorigenic risks. As effective carriers of intercellular signaling, they can transport various bioactive substances (such as miRNAs, mRNAs, proteins, and lipids), demonstrating significant advantages in regulating cellular functions within the musculoskeletal system, promoting tissue regeneration, and alleviating inflammation. This paper provides a systematic review of the research progress of MSC-derived EVs in musculoskeletal system diseases, focusing on their mechanisms of action and application potential in sarcopenia, osteoporosis, degenerative joint cartilage diseases, and tendon repair, aiming to provide theoretical basis and new research directions for related basic research and clinical translation.

Periodontal disease leads to progressive destruction of tooth-supporting tissues. Conventional therapies, such as open flap debridement, control inflammation but provide limited regeneration. Bioactive glass (BG), a bioactive and osteoconductive material, has emerged as a promising regenerative agent in periodontal therapy. This meta-analysis evaluated the clinical efficacy of BG in reducing probing depth (PD) and improving clinical attachment level (CAL) in periodontal lesions. A systematic search of Embase, PubMed, and Cochrane Library up to April 2025 identified randomized controlled trials (RCTs) assessing BG as a standalone intervention for periodontal regeneration. Studies reporting PD and/or CAL outcomes were included. Following Cochrane Collaboration standards, two reviewers independently extracted data and assessed bias risk. Meta-analysis using a random-effects model in RevMan (v5.4) addressed study heterogeneity. Twelve RCTs involving 234 patients and 406 periodontal defects were included. BG significantly improved PD reduction (MD = 1.27 mm; p = 0.0006) and CAL gain (MD = 1.49 mm; p = 0.0005), with moderate-to-high heterogeneity and no significant publication bias. These findings confirm that BG significantly enhances clinical outcomes in periodontal regeneration. Despite variability among studies, BG demonstrates strong potential as an effective regenerative material, warranting further high-quality trials.

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.

Background/Objectives: Systemic sclerosis (SSc) is a rare and severe autoimmune disease with limited treatment options. Autologous hematopoietic stem cell transplantation (HSCT) and mesenchymal stem cell transplantation (MSCT) have emerged as promising therapeutic strategies, especially for patients with refractory or rapidly progressive forms of the disease. However, no comparative synthesis has yet evaluated the clinical outcomes, safety, and applicability of these two distinct stem-cell-based interventions. This systematic review aimed to perform a comparative qualitative synthesis of clinical outcomes, safety profiles, and evidence quality for HSCT and MSCT in patients with systemic sclerosis, focusing on survival, skin fibrosis, pulmonary function, and adverse events. Methods: A comprehensive search was conducted in PubMed, ScienceDirect, Cochrane Library, and Google Scholar for the period between 2015 and May 2025. Studies were included if they reported on adult patients with a confirmed diagnosis of SSc treated with either autologous HSCT or MSCT and provided clinical outcome data. Risk of bias was assessed using the Newcastle-Ottawa Scale. Due to heterogeneity across studies, results were synthesized qualitatively. Results: Eleven studies met the inclusion criteria, comprising 504 patients (316 HSCT, 188 MSCT). HSCT showed consistent improvement in survival (1-, 5-, and 10-year), reduction in modified Rodnan skin scores (mRSS), and s ilization or improvement in pulmonary function (DLCO, FVC), albeit with a higher incidence of serious adverse events, including transplant-related mortality (up to 10%) and infectious complications. MSCT demonstrated favorable effects on skin fibrosis and lung involvement with a significantly lower toxicity profile. However, long-term survival data and methodological robustness were limited were more limited. HSCT was supported by multiple randomized controlled trials and international guidelines, while MSCT remains under clinical investigation with promising but still preliminary evidence. Conclusions: Both HSCT and MSCT demonstrate potential clinical benefits in systemic sclerosis, but they differ substantially in evidence strength and risk profiles. HSCT provides the most robust evidence for long-term disease modification in carefully selected patients, whereas MSCT represents a promising and safer investigational option, particularly for patients ineligible for intensive therapy. Further well-designed comparative studies are required to define their optimal clinical roles.

Although traumatic brain injury (TBI) is a significant cause of morbidity and mortality worldwide, there have been few significant therapeutic advances in recent years. Preclinical studies have explored the potential of adipose-derived stem cells (ADSCs) to improve neural function and reduce brain damage in animal models following TBI. This systematic review aims to assess and synthesize the current evidence on the efficacy of ADSCs in animal models with induced TBI.

Mesenchymal stem/stromal cell-derived extracellular vesicles (MSC-EVs) have emerged as promising cell-free therapeutics for breast cancer due to their innate tumor tropism and molecular delivery capacity. This systematic review and meta-analysis evaluated the in vitro therapeutic potential and safety of MSC-EVs. A comprehensive search up to July 2025 identified 58 eligible studies. Quantitative data were extracted on cell viability, apoptosis, and migration, along with EV source, cargo, and engineering strategy. Random-effects meta-analyses showed that MSC-EV treatment significantly reduced cancer cell viability (standardized mean difference [SMD] = -4.79), inhibited migration (SMD = -4.70), and increased apoptosis (SMD = +4.16). Effects were consistent across major cell lines (MCF-7, MDA-MB-231, and 4T1) and MSC sources (bone marrow, adipose, and umbilical cord), despite moderate heterogeneity (I2 = 50%-70%). Notably, unmodified bone marrow MSC-EVs carrying miR-23b were associated with dormancy induction in vivo, whereas engineered EVs loaded with therapeutic miRNAs or drugs and modified with targeting ligands demonstrated improved specificity and efficacy. Precision engineering of MSC-EVs can enhance antitumor activity but requires stringent cargo control to avoid dormancy risks. Only in vitro data were quantitatively analyzed, while in vivo findings were discussed for mechanistic context, providing a methodological foundation for future translational research.

Osteoarthritis (OA) and rheumatoid arthritis (RA) are chronic diseases characterized by persistent inflammation and autoimmune responses that affect the joints and other organs. Scientific evidence indicates that the therapeutic effects of mesenchymal stem cells (MSCs) are mediated through the release of soluble factors and extracellular vesicles (EVs), particularly exosomes. The release of microRNAs from MSCs holds substantial potential for cell-free treatment in OA and RA.

Crohn's disease (CD) is a chronic inflammatory bowel disease (IBD) that often leads to the development of complex perianal fistulas, significantly impairing patients' quality of life. Conventional medical and surgical treatments offer limited long-term efficacy, with high recurrence rates and associated complications. Adipose-derived stem cell therapy (ADSCT) has emerged as a promising regenerative therapy due to its anti-inflammatory and tissue-regenerative properties. However, discrepancies in clinical outcomes across studies warrant a systematic evaluation of its efficacy and safety.

Background: Autologous fat grafting (AFG) is increasingly explored beyond cosmetic applications, with interest in its regenerative potential for hand conditions such as cutaneous systemic sclerosis, thumb base osteoarthritis, Dupuytren contracture, burn scars, trauma and congenital hand deformities. This systematic review evaluates the therapeutic efficacy, techniques and outcomes associated with AFG across pathological hand conditions. Methods: A systematic literature search was conducted in July 2023 using PubMed, Ovid MEDLINE, Embase and Web of Science. Studies were included if they involved autologous fat or stromal vascular fraction (SVF) grafting for therapeutic purposes in hand conditions. Risk of bias (RoB) was assessed using RoB 2.0 for randomised controlled trials (RCTs) and the MINORS tool for non-RCTs. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed throughout. Results: Twenty-five studies were included (8 RCTs, 17 non-RCTs), involving a total of 909 patients. Conditions studied included systemic sclerosis (n = 7 studies), thumb base osteoarthritis (n = 7), Dupuytren contracture (n = 6), burn-related scars (n = 2), hand trauma (n = 2) and congenital deformities (n = 2). AFG was most consistently associated with improvements in pain (visual analogue scale [VAS]), joint mobility (range of motion) and functional scores such as the Cochin Hand Function Scale (CHFS), Quick Disabilities of the Arm, Shoulder and Hand (QuickDASH) and Michigan Hand Questionnaire (MHQ), particularly in systemic sclerosis and thumb base osteoarthritis. Findings in Dupuytren's contracture were mixed, with observational studies reporting early improvements but RCTs showing higher recurrence rates. Outcomes for burn scars, trauma and congenital deformities were less consistent. Techniques for fat harvesting, processing and injection varied widely. Conclusions: AFG shows therapeutic potential across several hand conditions, with the strongest current evidence supporting its use in systemic sclerosis and thumb base osteoarthritis. However, significant methodological heterogeneity and limited high-level evidence remain. Further robust, standardised RCTs are needed to clarify indications, optimise techniques and assess long-term outcomes. Level of Evidence: Level III (Therapeutic).

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.

Sarcoma refers to a broad type of cancer characterised by the abnormal growth of cells in connective tissues, bone, muscle, and cartilage. Although relatively rare, the survival rate of sarcoma patients is low primarily due to delayed diagnosis or metastasis at first presentation. Highly metastatic sarcoma has been suggested to be attributable to the presence of cancer stem cells (CSCs). Although a minor cell population, the stemness property renders CSCs stem cell-like characteristics. Nevertheless, CSCs presented a promising target towards advances in sarcoma therapy, particularly through stem cell reprogramming. Thus, this systematic review aims to gather existing studies on the methods of stem cell reprogramming that best produce sarcoma cancer stem cells (CSCs), which are crucial for understanding disease progression. An extensive literature search was conducted across four databases: PubMed, Wiley Online Library, Scopus, and ScienceDirect. The data obtained were synthesized and reported according to the following variables: types of cancer cells used for cancer stem cell generation, vector used for delivery of pluripotent genes, and CSCs maintenance medium. This systematic review demonstrated that cell dedifferentiation was independent of the cell sources. Furthermore, the addition of growth factors such as bFGF, EGF, or FGF significantly enhanced the formation of CSCs' spheroids. Most of the studies included in the review utilized a non-viral vector for the delivery of pluripotent gene markers into the cells.

Oral and maxillofacial diseases are often accompanied by tissue defects and damages, which are difficult to repair and affect patients both physically and psychologically as well as daily life. Recent 5 years studies have proved that stem cell-derived exosomes possess a broad clinical application in regenerative dentistry by promoting hard and soft tissue regeneration, angiogenesis, nerve repair, and wound healing, inhibiting inflammation and apoptosis, and modulating immune responses. The purpose of this review is to sum up the current state of research on stem cell-derived exosomes in periodontal regeneration and to discuss the current challenges and future directions.

This systematic review examines emerging delivery systems for bioactive molecules within regenerative endodontic therapy (RET) where hydrogels, nanogels, and polymeric nanoparticles along with advanced nanocarriers such as liposomes aquasomes, vesosomes, and mesoporous silica nanoparticles form the primary focus. The extensive literature search in PubMed, Scopus, and Web of Science databases (until August 2025) yielded a total of 47 eligible articles, including in vitro, ex vivo, animal, and a few clinical studies. Hydrogels emerged as a significant category, showcasing enhanced regenerative effects when used for the sustained release of various growth factors such as transforming growth factor-beta (TGF-β1), bone morphogenetic protein-2 (BMP-2), and vascular endothelial growth factor (VEGF). This was associated with improved angiogenesis and odontogenic differentiation. Nanogels exhibited high protein-loading efficiency and facilitated the differentiation of dental pulp stem cells, while polymeric nanoparticles demonstrated prolonged antibiotic and growth factor delivery with lower cytotoxicity. Among advanced nanocarriers, mesoporous silica nanoparticles showed promising potential for controlled release of growth factors and the formation of pulp-like tissues in animal models. In summary, the selected platforms for the delivery of bioactive molecules within RET show significant promise in terms of enhancing cell viability, bioactivity, and tissue regeneration. The findings indicate a practical pathway for clinicians aiming to achieve successful pulp-dentin tissue regeneration through translation research.

Toll/IL-1R (TIR) domain proteins, as central signaling hubs in innate immunity, dynamically orchestrate inflammatory responses and immune processes within the tumor microenvironment (TME) by mediating both MyD88-dependent and TRIF-dependent pathways. This review systematically elaborates on the dual regulatory roles of the TIR superfamily-encompassing toll-like receptors (TLRs), IL-1 receptors (IL-1Rs), and adaptor proteins-in tumor immunity, including the facilitation of stemness maintenance in cancer stem cells (CSCs) and the inductive mechanisms driving the formation of an immunosuppressive TME. From the perspective of clinical translation, the combinatorial therapeutic strategy of TIR agonists/inhibitors with immune checkpoint inhibitors (ICIs) represents a novel paradigm: the synergistic effects among TIR agonists/inhibitors, advanced nanodelivery systems, and radiotherapy-responsive prodrug technology provide a potential approach to address challenges such as systemic toxicity and low targeted delivery efficiency. Looking forward, the continuous advancement and broader application of TIR protein targets in the field of precision cancer immunotherapy hold great promise for offering new hope in the fight against malignant tumors.