Search Results (9,588)

Early-stage knee osteoarthritis (knee OA) lacks effective regenerative therapies. This study aimed to compare the cartilage regenerative effects, clinical efficacy, and safety of intra-articular injections of autologous adipose-derived mesenchymal stem cells (ADSCs) versus hyaluronic acid (HA). Forty-eight patients with early knee OA were enrolled in a prospective open-blinded multi-center study at Suranaree University of Technology Hospital and Phramongkutklao Hospital. Participants were randomized into either the ADSC or HA group. Primary outcomes included MRI-based cartilage lesion volume, synovial thickness via ultrasound, and WOMAC scores over 6 months. MRI results revealed significant and progressive cartilage regeneration in the ADSC group. In particular, medial femoral cartilage lesion volume decreased by 50.06 mm³, whereas the HA group showed an increase of 36.44 mm³. Synovial thickness also declined significantly in the ADSC group at 3 and 6 months. Both groups demonstrated reduced symptoms, but the ADSC group achieved superior and sustained improvements in WOMAC pain, stiffness, and function scores throughout the 6-month follow-up. The clinical benefits were consistent and more pronounced compared with HA. No serious adverse events occurred. In conclusion, intra-articular ADSC injections show superior cartilage restoration on MRI and better clinical outcomes than HA injection, making them a promising treatment for early-stage knee OA. Full article

Wound healing in oral surgery is influenced by systemic conditions (aging, diabetes) and habits (smoking, alcoholism), which can hinder the natural regenerative capacity of the oral mucosa. The human amniotic membrane (hAM), long recognized for its wound-healing properties, has gained attention as a valuable biomaterial in regenerative dentistry. Its biological composition—including epithelial and mesenchymal stem cells, collagen, growth factors, cytokines, and proteins with anti-inflammatory and antimicrobial properties—supports anti-inflammatory, angiogenic, immunomodulatory, and pro-epithelializing effects. These elements work synergistically to enhance tissue repair, reduce scarring, and promote rapid healing. The hAM can be preserved through cryopreservation, dehydration, or freeze-drying, maintaining its structural and functional integrity for diverse clinical uses. In oral surgery, the hAM has been applied with significant success to surgical wound coverage, treatment of periodontal and bone defects, and implant site regeneration, as well as management of complex conditions like medication-related osteonecrosis of the jaw (MRONJ). Clinical studies and meta-analyses support its safety, efficacy, and adaptability. Despite its proven therapeutic benefits, the hAM remains underutilized in dentistry due to challenges related to its preparation and storage. This review aims to highlight its potential and encourage broader clinical adoption in regenerative oral surgical practices. Full article

Time-lapse microscopy of mesenchymal stem cell (MSC) cultures allows for the quantitative observation of their self-renewal, proliferation, and differentiation. However, the rigorous comparison of two conditions, baseline (A) versus perturbation (B) (the addition of molecular factors, environmental shifts, genetic modification, etc.), remains difficult because morphology, division timing, and migratory behavior are highly heterogeneous at the single-cell scale. MSCs can be used as an in vitro model to study cell morphology and kinetics in order to assess the effect of, for example, gene therapy and prime editing in the near future. By combining static, frame-wise morphology with dynamic descriptors, we can obtain weight profiles that highlight which morphological and behavioral dimensions drive divergence. In this study, we present A/B Cells Policy: a modular, open-source Python package implementing a robust cell tracking pipeline. It integrates a YOLO-based architecture as a two-stage assignment framework with fallback and recovery passes, re-identification of lost tracks, and lineage reconstruction. The framework links descriptive statistics to a transferable system, opening up avenues for regenerative medicine, pharmacology, and early translational pipelines. It does this by providing an interpretable, measurement-based bridge between in vitro imaging and in silico intervention strategy planning. Full article

Breast cancer (BC) remains a leading cause of cancer-related mortality in women. Extracellular matrix (ECM) remodeling is a critical modulator of tumor invasion and metastasis. Three-dimensional (3D) cell culture models have been proposed as advanced systems better mimicking the tumor microenvironment (TME), potentially offering enhanced insights into underlying mechanisms compared to conventional two-dimensional (2D) cultures. This study highlights how BC cells develop metastatic potential and tumor progression independently from ECM contact using advanced 3D spheroid culture models compared to traditional 2D cultures in triple-negative breast cancer (TNBC) cell lines. Spheroids were formed using ultra-low adhesion plates, and their morphological and functional properties were assessed via phase-contrast and scanning electron microscopy (SEM), along with functional assays. Both cell lines formed compact spheroids exhibiting mesenchymal-to-epithelial transition (MET) characteristics. Functional assays showed enhanced cell migration and dissemination of spheroid-derived cancer cells. Gene expression profiling revealed increased expression of ECM remodeling enzymes, cell surface receptors, and adhesion molecules in 3D cultures compared to 2D. MicroRNA analysis highlighted distinct regulatory patterns specifically associated with metastasis and epithelial-to-mesenchymal transition (EMT). These findings demonstrate that 3D spheroid models effectively recapitulate the complexity of TNBC, providing valuable insights into ECM dynamics, epigenetic regulation, and metastatic behavior and potentially guiding improved therapeutic strategies. Full article

Acne vulgaris is a chronic disease that occurs in the pilosebaceous units and ranks eighth in the global prevalence of all diseases. In its severe forms such as pustules, cysts, and nodules, acne can lead to permanent scarring and post-inflammatory hyperpigmentation, which are often difficult to reverse in the short term and significantly affect patients’ psychological well-being and social interactions. Although a variety of pharmacological treatments are available, including retinoids, antibiotics, anti-androgens, benzoyl peroxide, and corticosteroids, the high recurrence rate and limited efficacy in scar prevention highlight the urgent need for innovative therapeutic strategies. Electrospinning technology has recently gained attention for fabricating nanofibrous patches with high porosity, biocompatibility, and biodegradability. These patches can offer antibacterial activity, absorb exudates, and provide mechanical protection, making them promising platforms for acne wound care. This review first outlines the pathophysiology of acne and the biological mechanisms underlying scar formation. We then present an overview of electrospinning techniques, commonly used polymers, and recent advancements in the field. Finally, we explore the potential of electrospun nanofibers loaded with mesenchymal stem cells or exosomes as next-generation therapeutic systems aimed at promoting scarless acne healing. Full article

High-risk (HR) neuroblastoma (NBL) patients often receive standardized treatment despite wide variations in clinical outcomes, underscoring the need for improved stratification tools. A distinguishing feature of NBL is the patient-specific expression of gangliosides (GGs), particularly GD2, which may serve as biomarkers. We analyzed GG profiles in 18 patient-derived tumors and 11 NBL cell lines using thin-layer chromatography and mass spectrometry. Expression of 0-, a-, and b-series GGs was examined and correlated with clinical risk, outcome, and gene expression data. Low-risk (LR) tumors expressed higher levels of complex b-series GGs. In HR tumors, five GG profiles (A–E) were identified. Profile A featured complex b-series GGs; B showed GD2 dominance; C showed synthesis arrest at GM3 or GD3 due to low expression of the GM2/GD2 synthase, encoded by the B4GALNT1 gene; D included complex a- and b-series GGs; and E was marked by GM2 and GD1a prevalence. B4GALNT1 expression served as a prognostic marker. Relapsed tumors following anti-GD2 therapy typically exhibited reduced GD2 levels, except for one profile A tumor that displayed a ceramide anchor shorter than those found in LR tumors. Astonishingly, the ceramide anchor composition of GD2 itself appears to separate LR and HR NBL, hinting at a role of ceramide synthases in NBL biology. All cell lines expressed GM2, but exhibited very low levels of complex b-series GGs. Profile C was found only in cell lines of the mesenchymal subtype. These findings support further investigation of GG composition and associated enzyme expression as potential biomarkers for risk stratification and treatment response in NBL. Full article

Adipose-derived mesenchymal stem cells (ASCs) have great potential in regenerative medicine due to their abundance and innate multi-lineage differentiation potential. However, the therapeutic efficacy of ASCs is often compromised by poor microenvironmental conditions in the damaged tissues after transplantation. In this study, we generated and assessed genetically modified ASCs that expressed granulocyte chemotactic protein-2 (GCP-2) and platelet-derived growth factor-β (PDGF-β). The results revealed that three-dimensional (3D)-cultured ASCs overexpressing GCP-2 and PDGF-β (3D-A/GP) yielded a significant increase in proangiogenic gene expression, cell migration, and endothelial tube formation in vitro. Moreover, the Matrigel plug assay revealed that 3D-A/GP formed functional blood vessels, and 3D-A/GP injection in a hind limb ischemia (HLI) model revealed higher blood flow recovery, limb salvage, and capillary density and lower apoptosis in mice, compared to the controls. Notably, 3D-A/GP exhibited differentiation into endothelial-like cells and upregulated expression of angiogenic factors in ischemic limb tissue. Our results highlight the value of using a combination of genetic engineering and 3D culture systems to improve the therapeutic effect of ASCs in terms of angiogenesis-dependent tissue repair. The dual modulation of GCP-2 and PDGF-β, in combination with 3D culture, presents a new and synergistic opportunity to maximize the use of ASC-based therapies for ischemic diseases and other regenerative medicine applications. Full article

Postnatal stem cells are crucial for tissue homeostasis and repair and are regulated by specialized microenvironmental microterritories known as “stem cell niches”. Proposed by R. Schofield in 1978 for hematopoietic stem cells, niches maintain self-renewal, guide differentiation and maturation, and can even revert progenitor cells to an undifferentiated state. Niches respond to injury, oxygen levels, mechanical cues, and signaling molecules. While the niche concept has advanced regenerative medicine, bioengineering, and 3D bioprinting, further progress is hindered by inconsistent interpretations of its core principles. To address this, we proposed a consensus-building initiative among experts in regenerative medicine and bioengineering. We have developed a questionnaire covering the niche topography, hierarchy, dimension, geometry, composition, regulatory mechanisms, and specifically the mesenchymal stem cell niches. This pilot survey, being conducted under the auspices of the National Society for Regenerative Medicine in the Russian Federation, aims to establish a standardized framework on the eve of the 50th anniversary of Schofield’s hypothesis. The resulting consensus will guide future research and innovation in this pivotal field. Full article

Human mesenchymal stem cells (hMSCs) and their secreted extracellular vesicles (EVs) are promising therapeutics to treat degenerative or inflammatory diseases such as ischemic stroke and Alzheimer’s disease (AD). hMSC-EVs have the coveted ability to contain therapeutically relevant biomaterials; however, EV biogenesis is sensitive to the culture microenvironment in vitro. Recently, the demand for hMSC-EVs has increased dramatically, highlighting the need for scalable bioreactors for large-scale biomanufacturing. In this study, adipose-derived hMSCs were seeded in 2D plates, an ultralow-attachment (ULA) plates as static aggregates, a novel vertical wheel bioreactor (VWBR) as aggregates, and a spinner flask bioreactor (SFB). EV secretion was quantified and compared using ExtraPEG-based ultracentrifugation and nanoparticle tracking analysis. Compared to the 2D group, significantly higher total EV production and cell productivity in the bioreactors were observed, as well as the upregulation of EV biogenesis genes. Furthermore, there was increased EV production in the VWBR compared to the SFB and the static ULA control. Functional assessments demonstrated that EVs, when delivered via culture medium or hydrogel-based systems, significantly attenuated oxidative stress elevation, suppressed proinflammatory cytokine secretion (e.g., TNF-α) and gene expression, and inhibited nuclear factor kappa-light-chain-enhancer of activated B-cell (NF-κB) activation and neurodegenerative markers across in vitro assays. These findings suggest EV-mediated mitigation of oxidative and inflammatory pathways, potentially through modulation of the NF-κB signaling cascade. This study shows the influence of bioreactor types and their microenvironments on EV secretion in hMSCs and their applications in hMSC-EV production and bioengineering. Full article

Background: Major depression is a significant source of suffering and economic loss. Despite efforts to understand this condition and find better treatments, the burden imposed by this disease continues to rise. Most approved pharmacological treatments for depression focus on controlling the availability of monoamines in synapses. However, accumulating evidence suggests that neuroinflammation, oxidative stress, and reduced hippocampal neurogenesis play key roles as causal factors in the development of major depression symptoms. Therefore, preclinical testing of pharmacological approaches targeting these factors is essential. Mesenchymal stem cells (MSCs) are known for their potential as powerful antioxidants and anti-inflammatory agents, exerting neuroprotective actions in the brain. They produce various therapeutic molecules in a paracrine manner, collectively known as secretome. Methods: In this work, we evaluated the antidepressant potential of repeated intranasal administration of MSC-derived secretome in an animal model of major depressive disorder induced by chronic mild unpredictable stress. Results: We observed that intranasal administration of MSC-derived secretome reduced the appearance of some of the behavioral parameters commonly associated with major depression, including anhedonic, apathetic, and anxious behaviors, inducing a strong reduction in the overall depression score compared to vehicle-treated animals. At the structural level, secretome administration prevented increased astrocyte density and the atrophy of astrocyte processes observed in vehicle-treated stressed animals. Additionally, secretome administration induced an increase in myelin levels and oligodendroglia in the cortex. Conclusions: Our data suggests that intranasal administration of MSC-derived secretome may represent a potential therapeutic alternative to current treatments for this devastating pathology. Full article

Periodontal therapy remains a complex task in dentistry as current methodologies often tend to induce tissue repair rather than regeneration. Caffeine is an alkaloid found in multiple natural sources, which has been reported to have multiple beneficial effects, such as promoting adipogenic differentiation, a key factor in tissue regeneration. Unfortunately, it has also been reported to decrease cell viability and reduce osteogenic and chondrogenic differentiation, both of which play an important role in regenerative medicine. In this study, we aimed to find a non-cytotoxic dose of purified caffeine over dental pulp stem cells (DPSCs) that could provide its beneficial effects over adipogenesis, while reducing the negative effect upon osteogenesis and chondrogenesis. Additional experiments were conducted to determine its impact upon the expression of pro-inflammatory enzymes, and antibacterial assays to assess a potential antibacterial effect. The results attested that purified caffeine at a dose of 8.03 μM holds no viability reduction effect, nor has any impact on the expression of pro-inflammatory enzymes, promotes adipogenic differentiation, and does not negatively affect osteogenic or chondrogenic differentiation, with any antibacterial effect against Streptococcus mutans, Escherichia coli, and Staphylococcus aureus. These findings suggest that purified caffeine at a dose of 8.03 μM has the potential to aid in the field of regenerative dentistry. Full article

This review article provides a comprehensive evaluation of Infuse^® and InductOs^®, two ground-breaking recombinant human Bone Morphogenetic Protein-2 (rhBMP-2)-based bone graft products, focusing on their tissue-level regenerative responses, clinical applications, and associated costs. Preclinical and clinical studies demonstrate that rhBMP-2 induces strong osteoinductive activity, effectively promoting mesenchymal stem cell differentiation and vascularized bone remodeling. While generally well-tolerated, these osteoinductive effects are dose-dependent, and excessive dosing or off-label use may result in adverse outcomes, such as ectopic bone formation or soft tissue inflammation. Histological and imaging analyses in craniofacial, orthopedic, and spinal fusion models confirm significant bone regeneration, positioning rhBMP-2 as a viable alternative to autologous grafts. Notably, advances in delivery systems and scaffold design have enhanced the stability, bioavailability, and targeted release of rhBMP-2, leading to improved fusion rates and reduced healing times in selected patient populations. These innovations, alongside its proven regenerative efficacy, underscore its potential to expand treatment options in cases where autografts are limited or unsuitable. However, the high initial cost, primarily driven by rhBMP-2, remains a critical limitation. Although some studies suggest overall treatment costs might be comparable to autografts when factoring in reduced complications and operative time, autografts often remain more cost-effective. Infuse^® has not substantially reduced the cost of bone regeneration and presents additional safety concerns due to the rapid (burst) release of growth factors and limited mechanical scaffold support. Despite representing a significant advancement in synthetic bone grafting, further innovation is essential to overcome limitations related to cost, mechanical properties, and controlled growth factor delivery. Full article

Background/Objectives: Psoriasis is a chronic systemic inflammatory disease. Evidence on the efficacy of different mesenchymal stem cell (MSC) exosomes for psoriasis remains limited. This study aimed to evaluate the therapeutic effects of different MSC exosomes in mitigating psoriasis. Methods: The efficacy of human placenta MSC (hPMSC) and human umbilical cord MSC (hUCMSC) exosomes was compared in an imiquimod (IMQ)-induced psoriasis murine model. A meta-analysis was performed to incorporate the results of studies using IMQ-induced psoriasis murine models to compare MSC exosome treatments (exosome group) with vehicle or no-treatment controls (control group). Results: In this murine study, both the hPMSC and hUCMSC exosomes showed better effectiveness in reducing epidermal thickness and skin tissue cytokines than controls, but no significant difference was observed between the two MSC exosomes. Seven studies were included in the meta-analysis. Clinical severity scores were significantly lower in the exosome group than in the controls (standardized mean difference [SMD]: −1.886; 95% confidence interval [CI]: −3.047 to −0.724). Epidermal thickness was significantly reduced (SMD: −3.258; 95% CI: −4.987 to −1.529). No significant differences were found in most skin cytokines between the groups, although tumor necrosis factor-α mRNA (SMD: −0.880; 95% CI: −1.623 to −0.136) and interleukin-17A protein levels (SMD: −2.390; 95% CI: −4.522 to −0.258) were both lower in the exosome group. Meta-regression revealed a greater improvement in clinical scores in studies using hUCMSC exosomes compared to other MSC sources (p = 0.030). Conclusions: hUCMSC exosomes have been studied more extensively than other MSC exosomes. MSC exosomes reduce clinical severity and epidermal hyperplasia. Full article

Prostate cancer (PCa) progression is shaped by the tumour microenvironment, where hypoxia promotes aggressiveness and contributes to therapy resistance. Extracellular vesicles (EVs), secreted under hypoxia, can deliver modified bioactive cargo that reprograms recipient cells. This study examined whether EVs from hypoxia-conditioned metastatic PCa cells enhance malignant traits in cancerous and non-tumorigenic prostate cell lines via Wnt signalling and epithelial–mesenchymal transition (EMT). EVs from PC3 cells cultured under hypoxia (1% O₂) or normoxia (21% O₂) as control were applied to LNCaP (low metastatic potential) and PNT2 (non-tumorigenic) cells. PC3 hypoxia-derived EVs increased HIF-1α, upregulated mesenchymal markers (Vimentin, N-cadherin) and Wnt-related genes (Wnt3A, Wnt5A, Fzd7), and suppressed the epithelial marker E-cadherin. Functional assessment showed that LNCaP cells treated with PC3 hypoxia EVs showed greater motility and invasiveness, and PNT2 cells displayed transcriptomic reprogramming. These findings show that hypoxia-driven EVs can propagate pro-metastatic signalling in less aggressive and normal prostate cells. The findings highlight EVs as a potential therapeutic target in PCa progression. Full article

Acute myeloid leukemia (AML) proliferation is significantly influenced by the interactions between leukemia blasts and the bone marrow (BM) microenvironment. Specifically, bone marrow mesenchymal stem cells (BMSCs) derived from AML patients (AML-MSCs) are known to support leukemia growth and facilitate disease progression. Studies have demonstrated that the transfer of mitochondria from MSCs to AML blasts not only aids in disease progression but also contributes to chemotherapy resistance. Furthermore, BM stromal cells can trigger a metabolic shift in malignant cells from mitochondrial respiration to glycolysis, which enhances both growth and chemo-resistance. This study focuses on identifying transcriptional and metabolic alterations in AML-MSCs to uncover potential targeted therapies for AML. We employed RNA sequencing and microarray analysis on MSCs cocultured with leukemic cells (MLL-AF9) and on MSCs isolated from both non-leukemic and MLL-AF9 leukemic mice. The Gene Set Enrichment Analysis (GSEA) indicated a significant downregulation of gene sets associated with oxidative phosphorylation and glycolysis in AML-MSCs. Furthermore, coculture of MSCs from wild-type mice (WT-MSCs) and a healthy donor individual (HD-MSCs) with AML cells demonstrated reduced oxidative phosphorylation and glycolysis. These metabolic changes were consistent in AML-MSCs derived from both leukemic mice and patients. Our results indicate that AML cells diminish the metabolic capacity of MSCs, specifically targeting oxidative phosphorylation and glycolysis. These findings suggest potential metabolic vulnerabilities that could be exploited to develop more effective therapeutic strategies for AML. Full article