Search Results (1,536)

(1) Background: The present study investigated the effects of extracellular vesicles (EVs), derived from adipose tissue stem cells (ADSCs) and bone marrow mesenchymal stem cells (BMMSCs), on atherosclerosis-associated cardiac hypertrophy. (2) Methodology: The experiments were performed on hamsters divided into the following groups: control (C) fed with a standard diet; hypertensive–hyperlipidemic (HH) generated by combining a diet enriched with 3% cholesterol, 15% butter, and by gavage with 8% NaCl on a daily basis; HH groups injected with EVs (ADSCs) or EVs (BMMSCs), either transfected with Smad2/3 siRNAs or not (HH-EVs (ADSCs), HH-EVs (BMMSCs), HH-EVs (ADSCs) + Smad2/3siRNA, HH-EVs (BMMSCs) + Smad2/3siRNA); and HH group injected with Smad2/3 siRNAs (HH-Smad2/3siRNA). (3) Results: In comparison with the HH group, the findings demonstrated that treatment using EVs (ADSCs or BMMSCs), either with or without Smad2/3 siRNAs, resulted in several significant improvements in the following aspects: the plasma levels of cholesterol, LDL, triglycerides, TGF-β1, and Ang II were decreased; the left ventricular structure and function were recovered; inflammatory markers, ROS, COL1A, α-SMA, Cx43, MIF, ANF, and M1/M2 macrophages, were reduced; the level of key protein NF-κB p50 was diminished. (4) Conclusions: These findings underscore the therapeutic potential of mesenchymal stem cell-derived EVs in atherosclerosis-associated cardiac hypertrophy. Full article

Adipose tissue plays a crucial role in the tumor microenvironment (TME), where its secreted extracellular vesicles (EVs) are involved in the complex signaling between tumor cells and surrounding stromal components. This study aims to unravel the mechanisms through which adipocyte-derived EVs influence breast cancer (BC) progression. Human mesenchymal stem cells (hMSCs) were differentiated into adipocytes following a 21-day induction protocol that led to significant accumulation of lipid droplets within the cells. EVs were isolated from the conditioned medium of both hMSC-derived adipocytes and BC cells. Particle size distribution, morphology, and uptake into the recipient cell were investigated via nanoparticle tracking analysis, transmission electron microscopy, and fluorescence microscopy, respectively. Our results show that BC-derived EVs notably impaired cell viability and modulated the expression of key genes involved in apoptosis resistance within stromal cells. On the other hand, stromal-derived EVs significantly altered tumor cell behavior, indicating a dynamic, bidirectional exchange of bioactive signals. These findings underscore the pivotal role of EV-mediated communication in the tumor-stroma interplay, suggesting that adipocyte-cancer cell EV crosstalk contributes to the remodeling of the TME, potentially facilitating tumor progression. Full article

Adipose tissue renewal requires precise coordination of stem/progenitor cell proliferation, preadipocyte commitment, and terminal adipocyte differentiation. T-cadherin (CDH13), an atypical GPI-anchored cadherin, is expressed in adipose tissue and functions as a receptor for high-molecular-weight (HMW) adiponectin—a key adipokine produced by adipose tissue and involved in metabolic regulation. While T-cadherin is implicated in cardiovascular and metabolic homeostasis, its role in adipogenesis still remains poorly understood. In this study, we used the 3T3-L1 preadipocyte model to investigate the function of T-cadherin in adipocyte differentiation. We analyzed T-cadherin expression dynamics during differentiation and assessed how T-cadherin overexpression or knockdown affects lipid accumulation, expression of adipogenic markers, and key signaling pathways including ERK, PI3K–AKT, AMPK, and mTOR. Our findings demonstrate that T-cadherin acts as a negative regulator of adipogenesis. T-cadherin overexpression ensured a proliferative, undifferentiated cell state, delaying early adipogenic differentiation and suppressing both lipid droplet accumulation and the expression of adipogenic markers. In contrast, T-cadherin downregulation accelerated differentiation, enhanced lipid accumulation, and increased insulin responsiveness, as indicated by PI3K–AKT pathway activation at specific stages of adipogenesis. These results position T-cadherin as a key modulator of adipose tissue plasticity, regulating the balance between progenitor expansion and terminal differentiation, with potential relevance to obesity and metabolic disease. Full article

This narrative review synthesizes PubMed- and Scopus-indexed studies from 2020 to 2025, including preclinical animal models, prospective cohort studies, and level I and II randomized trials, to compare two leading biologic augmentation strategies: platelet-rich plasma (PRP) and bone marrow aspirate concentrate (BMAC). The review examines underlying mechanisms of action, delivery techniques, imaging biomarkers of graft maturation, patient-reported and functional outcomes, safety profiles, cost-effectiveness, and regulatory frameworks. PRP provides early anti-inflammatory and proangiogenic signaling, while BMAC delivers a concentrated population of mesenchymal stem cells and growth factors to the tendon–bone interface. Both modalities consistently enhance MRI-defined graft maturation, yet evidence of long-term functional or biomechanical superiority remains inconclusive. Emerging therapies such as peptide hydrogels, adipose-derived stem cells, and exosome delivery offer promising avenues for future research. Standardized protocols and large multicenter trials are needed to clarify comparative efficacy and inform personalized rehabilitation strategies. Full article

Neural tissue injuries, including spinal cord damage and neurodegenerative diseases, pose a major clinical challenge due to the central nervous system’s limited regenerative capacity. Current treatments focus on stabilization and symptom management rather than functional restoration. Tissue engineering offers new therapeutic perspectives, particularly through the combination of electrospun nanofibrous scaffolds and mesenchymal stem cells (MSCs). Electrospun fibers mimic the neural extracellular matrix, providing topographical and mechanical cues that enhance MSC adhesion, viability, and neural differentiation. MSCs are multipotent stem cells with robust paracrine and immunomodulatory activity, capable of supporting regeneration and, under proper stimuli, acquiring neural-like phenotypes. This systematic review, following the PRISMA 2020 method, analyzes 77 selected articles from the last ten years to assess the potential of electrospun biopolymer scaffolds for MSC-mediated neural repair. We critically examine the scaffold’s composition (synthetic and natural polymers), fiber architecture (alignment and diameter), structural and mechanical properties (porosity and stiffness), and biofunctionalization strategies. The influence of MSC tissue sources (bone marrow, adipose, and dental pulp) on neural differentiation outcomes is also discussed. The results of a literature search show both in vitro and in vivo enhanced neural marker expression, neurite extension, and functional recovery when MSCs are seeded onto optimized electrospun scaffolds. Therefore, integrating stem cell therapy with advanced biomaterials offers a promising route to bridge the gap between neural injury and functional regeneration. Full article

Background: Sarcopenia is characterized by a loss of muscle mass and strength, resulting in functional limitations and an increased risk of falls, injuries and fractures. The aim of this study was to obtain detailed information on skeletal muscle changes in patients with multiple myeloma (MM) during treatment. Methods: A total of 51 patients diagnosed with MM who had undergone whole-body low-dose computed tomography acquisition prior to induction therapy (T1) and post autologous stem cell transplantation (T2) were examined retrospectively. Total volume (TV), muscle volume (MV) and intramuscular adipose tissue volume (IMAT) of the autochthonous back muscles, the iliopsoas muscle and the gluteal muscles were evaluated on the basis of the resulting masks of the BOA tool with the fully automated combination of TotalSegmentator and a body composition analysis. An in-house trained artificial intelligence network was used to obtain a fully automated three-dimensional segmentation assessment. Results: Patients’ median age was 58 years (IQR 52–66), 38 were male and follow-up CT-scans were performed after a mean of 11.8 months (SD ± 3). Changes in MV and IMAT correlated significantly with Body-Mass-Index (BMI) (r = 0.7, p < 0.0001). Patients (n = 28) with a decrease in BMI (mean −2.2 kg/m²) during therapy lost MV (T1: 3419 cm³, IQR 3176–4000 cm³ vs. T2: 3226 cm³, IQR 3014–3662 cm³, p < 0.0001) whereas patients (n = 20) with an increased BMI (mean +1.4 kg/m²) showed an increase in IMAT (T1: 122 cm³, IQR 96.8–202.8 cm³ vs. T2: 145.5 cm³, IQR 115–248 cm³, p = 0.0002). Loss of MV varied between different muscle groups and was most prominent in the iliopsoas muscle (−9.8%) > gluteus maximus (−9.1%) > gluteus medius (−5.8%) > autochthonous back muscles (−4.3%) > gluteus minimus (−1.5%). Increase in IMAT in patients who gained weight was similar between muscle groups. Conclusions: The artificial intelligence-based three-dimensional segmentation process is a reliable and time-saving method to acquire in-depth information on sarcopenia in MM patients. Loss of MV and increase in IMAT were reliably detectable and associated with changes in BMI. Loss of MV was highest in muscles with more type 2 muscle fibers (fast-twitch, high energy) whereas muscles with predominantly type 1 fibers (slow-twitch, postural control) were less affected. This study provides valuable insight into muscle changes of MM patients during treatment, which might aid in tailoring exercise interventions more precisely to patients’ needs. Full article

Urethral stricture involves fibrotic narrowing of the urethral mucosa and spongiosum. Although urethroplasty using oral mucosal grafts is the gold standard for complex cases due to its high success rate, technical complexity limits its broader adoption. To address this, endoscopic transplantation of oral mucosal tissue has been proposed. While feasibility has been demonstrated, clinical efficacy remains suboptimal. Developing adjunctive factors that facilitate mucosal engraftment may improve outcomes of endoscopic transplantation. Extracellular vesicles (EVs)—membrane-bound nanoparticles secreted by cells that deliver miRNAs and other bioactive molecules—have recently emerged as promising candidates. We investigated EVs derived from four mesenchymal stromal cell (MSC) sources—stem cells from human exfoliated deciduous teeth (SHED), adipose tissue, umbilical cord, and bone marrow (BM)—isolated during both logarithmic (log) and stationary culture phases. miRNA profiling revealed distinct phase- and origin-specific signatures. SHED-derived EVs from the log phase and bone marrow-derived EVs from the stationary phase expressed miR-31, the let-7 family, and miR-205, suggesting early wound healing potential. In contrast, stationary-phase SHED-EVs and log-phase BM-MSC-EVs were enriched in the miR-99 family and miR-31, indicating potential roles in epithelial stabilization and fibrosis modulation. These findings support phase-specific application of MSC-EVs to optimize mucosal engraftment in transurethral reconstruction. Full article

Heterotopic ossification (HO) is a disease characterized by ectopic bone formation, which can occur following severe traumatic brain injury (TBI). However, the underlying mechanisms remain poorly understood. In this study, we established a stem cell model using adipose-derived stem cells (ADSCs) and skeletal stem cells (SSCs) to examine osteogenic factors present in the sera of TBI patients. Incubation of ADSCs and SSCs with osteoinductive medium supplemented with TBI serum significantly enhanced osteogenic differentiation, particularly in male ADSCs and both female and male SSCs, with male SSCs exhibiting the highest osteogenic potential. Furthermore, we identified TGF-β1 as an important factor involved in these osteogenic processes. Elevated levels of TGF-β1 were detected in the serum of male TBI patients 14 days post-injury. Cellular assays revealed a sexual dimorphism in response to TGF-β1 neutralization: osteogenic differentiation in male SSCs was significantly reduced, while no effect was detectable in female SSCs. These findings, together with the rarity of HO in female patients, suggest that TGF-β1 plays a central role in the development of HO in males. Furthermore, this study highlights the importance of considering sex-specific mechanisms in traumatic HO for the development of sex-specific therapy options. Full article

The endocannabinoid system regulates key biological functions such as neuroprotection, pain modulation, inflammation, and immunomodulation. Cannabis-based therapies have gained attention due to the therapeutic potential of their bioactive compounds, particularly phytocannabinoids like cannabidiol (CBD), which exhibit anti-inflammatory, neuroprotective, and immunomodulatory properties. Mesenchymal stem cells (MSCs) are widely studied for their regenerative and immunomodulatory potential. This study evaluated the effects of priming canine adipose tissue-derived MSCs (cAT-MSCs) with a CBD-rich cannabis extract on cell morphology, viability, neurotrophic factor gene expression, and cytokine gene and protein expression. cAT-MSCs (n = 5) were primed for 24 h and divided into three groups: Control (C, unprimed), D1 (2.25 µM CBD), and D2 (225 nM CBD). No morphological or viability changes were observed. Gene expression analysis showed that groups D1 and D2 exhibited increased HGF expression. D1 also showed increased IDO and decreased BDNF expression. In contrast, no significant changes were observed in GDNF, IL-10, TNF-α, IFN-γ, or PTGES2. Regarding the cytokine profile, GM-CSF, IL-2, and IL-10 were undetectable. Notably, IL-8 and MCP-1 levels were significantly reduced in D1 compared to the control. These findings suggest that CBD priming modulates key regenerative and inflammatory mediators in cAT-MSCs, supporting its potential application in enhancing the efficacy of cell-based therapies. Full article

Mesenchymal stem cells (MSCs) spontaneously assemble into three-dimensional (3D) spheroids under matrix-deficient conditions such as the synovial cavity, although their functional significance has yet to be fully elucidated. In this study, we used concave microwell cultures to promote the spontaneous aggregation of adipose-derived MSCs (ASCs) from OA patients, thereby mimicking the intra-articular microenvironment. We analyzed the paracrine factors of ASC aggregates and compared it with that of conventional 2D monolayer cultures. Notably, 3D aggregation significantly increased the secretion of HGF and VEGF, whereas FGF2 levels remained relatively unchanged. These results indicate that the structural characteristics of ASC aggregates enhance the secretion of key paracrine factors involved in angiogenesis and tissue repair. To functionally evaluate the biological relevance of the secreted factors, conditioned media (CM) from ASC aggregates were applied to human articular chondrocytes. The CM significantly promoted chondrocyte proliferation, an effect that was abolished by the addition of HGF-neutralizing antibodies, thereby highlighting HGF as a central mediator of the regenerative response. Additionally, we further explored whether extracellular factors could modulate growth factor expression such as HGF. In this context, we investigated the impact of low-concentration hyaluronic acid (HA), a key synovial component widely used in OA treatment. Co-treatment with HA not only amplified the expression and secretion of HGF, VEGF, and FGF2, but also promoted ASC proliferation. ASCs forming functional aggregates may exert regenerative effects as active paracrine modulators, and the addition of low-dose hyaluronic acid is expected to further enhance this function, offering a promising strategy for MSC-based osteoarthritis therapy. Full article

Background: Scar management remains a significant challenge in plastic and reconstructive surgery, particularly when addressing atrophic, retractile, or fibrotic scars. Autologous fat grafting and hybrid fractional laser therapy have independently shown efficacy in improving scar quality. This study aims to evaluate the synergistic effect of their combination on clinical and functional scar outcomes. Methods: A prospective, comparative study was conducted on patients with cutaneous scars of various etiologies. Participants were treated with either hybrid fractional laser therapy alone (CO₂ and 1570 nm Erbium-glass wavelengths) or a combined protocol of laser plus autologous lipofilling. Clinical outcomes were assessed at baseline and at 30, 60, and 90 days post-treatment using the Vancouver Scar Scale (VSS), patient satisfaction scores, and Visual Analog Scale (VAS) for pain and discomfort. Results: Patients receiving the combined treatment demonstrated significantly greater improvement in scar pigmentation, elasticity, pliability, and thickness compared to those treated with laser alone. Subjective symptoms, including pain and itching, were also more effectively alleviated. The volumetric and regenerative properties of adipose tissue, particularly its content of adipose-derived stem cells (ADSCs) and stromal vascular fraction (SVF), likely contributed to the enhanced outcomes observed. Conclusions: The combination of hybrid fractional laser therapy and autologous lipofilling offers a superior therapeutic strategy for scar remodeling compared to laser monotherapy. This integrated regenerative approach addresses both structural and biological aspects of scar tissue, making it a valuable protocol for personalized and effective scar management. Further randomized trials with larger sample sizes and histological validation are warranted to confirm these preliminary findings and refine therapeutic protocols. Full article

In our previous study, adipose-derived stem cells (ASCs) cultured in a three-dimensional (3D) organotypic system exhibited mesenchymal-to-epithelial transition (MET) features, including cobblestone morphology and increased expression of E-cadherin and CK18. In this study, we investigated whether ionizing radiation could reverse this phenotype via epithelial–mesenchymal transition (EMT) and examined the involvement of Notch signaling. Mouse ASCs were cultured in Matrigel-based 3D organotypic conditions and exposed to 8 Gy of γ-radiation, and EMT- and Notch-related gene and protein expression were assessed 96 h post-irradiation using ATP viability assays, RT-qPCR, and Western blotting. Exposure to 8 Gy significantly reduced cell viability in 2D ASCs to 49.50 ± 6.50% compared with 61.02 ± 5.77% in 3D organoids (p < 0.0001). Irradiated 3D organoids showed EMT-like changes, including an increase of ~2.5-fold in fibronectin and an increase of ~2.0-fold in Twist1 expression, while epithelial CK18 was modestly elevated. Notch signaling was concurrently activated, with Notch1 and Jagged1 increasing by more than twofold and Fra-1 being significantly upregulated. Pretreatment with 20 μM of the γ-secretase inhibitor (GSI) kept cell viability above 90% and suppressed radiation-induced fibronectin, Twist1, Notch1, and Jagged1 expression. These findings indicate that ionizing radiation promotes EMT in 3D-cultured ASCs and reverses prior epithelialization, with Notch signaling playing a key regulatory role. The 3D ASC organoid model may thus provide a physiologically relevant platform for investigating radiation-induced plasticity and potential antifibrotic interventions. Full article

Human stem cell research is entering a stage where disease modeling, translational applications, and clinical therapies are increasingly connected. This editorial provides an overview of the contributions included in this Special Issue, titled “Human Stem Cells in Disease Modelling and Treatment”, placing them within the wider landscape of stem cell science. We summarize advances in ovarian stem cells for infertility, mesenchymal stem cells for neurodegeneration, pluripotent stem cell-derived cardiovascular and kidney organoids, adipose-derived stem cells, and emerging immunomodulatory and neural progenitor approaches. These studies illustrate the breadth of stem cell research and its potential to inform clinical practice. At the same time, challenges remain in reproducibility, safety, scalability, and ethical oversight. Looking forward, collaborative work and harmonized global standards will be important to bring laboratory findings into therapies that are safe, effective, and accessible. This editorial closes the first edition of the Special Issue with a reflection on current progress and directions for the future. Full article

Background: Knee osteoarthritis (OA) is a leading cause of disability, with limited therapies that modify both symptoms and structural degeneration. Autologous microfragmented adipose tissue (MFAT) has emerged as a promising regenerative option, especially in phenotypically distinct OA subgroups. This randomized controlled trial evaluated the clinical and structural efficacy of intra-articular MFAT versus hyaluronic acid (HA) in patients with early to moderate inflammatory phenotype knee OA. Methods: Fifty-three patients were randomized in a 2:1 ratio to receive either MFAT (n = 35) or HA (n = 18). Patients were followed-up for six months post-injection and evaluated using patient-reported outcome measures (KOOS, WOMAC, VAS) and delayed gadolinium-enhanced MRI of cartilage (dGEMRIC). A responder analysis defined structural response as ≥10% increase in dGEMRIC in ≥3 of 7 predefined cartilage regions. Results: Both MFAT and HA led to statistically significant improvements in clinical scores and cartilage glycosaminoglycan content. MFAT showed greater mean improvements across most clinical and dGEMRIC measures, although without reaching statistical significance, except for KOOS Symptoms (MFAT: +25.0 vs. HA: +12.7, p = 0.008). Responder-level analysis revealed that all patients who demonstrated structural response also experienced clinically meaningful pain improvement (KOOS Pain ≥ 10), while no patient showed structural benefit without parallel symptomatic relief. Conclusions: MFAT led to greater improvement in symptoms related to joint stiffness, swelling, and crepitus compared to HA, reflecting its potential benefit in targeting the inflammatory features of knee OA. Importantly, HA also led to significant clinical and structural improvements, supporting its continued role as a standard-of-care comparator in knee OA management. Furthermore, the correlation between dGEMRIC and clinical response suggests its utility as a predictive biomarker of treatment success. Full article

Background/Objectives: Knee osteoarthritis (OA) is a major cause of pain and functional disability worldwide, leading to a growing interest in more durable and less invasive therapies. Micro-fragmented adipose tissue (MFAT) injections have emerged as a promising frontier in regenerative therapies using mesenchymal stem cells (MSCs). This study assessed the safety and effectiveness of MFAT injections for symptomatic knee OA while investigating the duration of treatment effects. Methods: This longitudinal study screened patients with symptomatic Kellgren-Lawrence (KL) grade II-IV knee OA who received single-dose MFAT injections. Outcomes were assessed using the Knee injury and Osteoarthritis Outcome Score (KOOS) subscales at baseline, 3, 6, and 12 months. A linear mixed effects model was performed to explore how age, BMI, sex, and OA severity influence outcomes. Results: Among 39 evaluable patients, mean baseline KOOS was 46.5 (SD 18.1). KOOS scores improved significantly across all subscales, peaking at six months and remaining higher than baseline at 12 months. Improvements exceeded clinically meaningful thresholds, including KL grades IV. Female patients reported significantly worse overall outcomes than male patients (p < 0.05). Minor self-limiting synovitis was reported in 18% of cases, and no severe adverse events were observed. Conclusions: MFAT infiltration may represent a safe, minimally invasive option to improve symptoms and delay surgery in patients with knee OA, including those with advanced disease. These findings highlight the potential role of MFAT as part of the treatment algorithm for knee OA, although strategies to sustain long-term benefits and confirmatory trials are needed. Full article