Search Results (729)

Background: Mesenchymal stem cells (MSCs), multipotent and immune-regulatory cells derived from tissues such as bone marrow, dental pulp, and periodontal ligament, emerged as promising agents in regenerative dentistry. Their clinical applications include endodontic tissue regeneration, periodontal healing, and alveolar bone repair, addressing critical challenges in dental tissue restoration. Methods: A systematic review was conducted following PRISMA guidelines and registered in PROSPERO. We searched PubMed, Scopus, and Web of Science databases for open-access, English-language clinical trials and observational studies published from 2015 to 2025. Studies focusing on the application of MSCs in dental tissue regeneration were included based on predefined eligibility criteria. Results: Out of 2400 initial records, 13 studies met the inclusion criteria after screening and eligibility assessment. Most studies investigated MSCs derived from dental pulp and periodontal ligament for regenerating periodontal tissues and alveolar bone defects. The majority reported improved clinical outcomes; however, variations in MSC sources, delivery methods, sample sizes, and follow-up periods introduced methodological heterogeneity. Conclusions: MSCs show significant potential in enhancing bone and periodontal regeneration in dental practice. Nonetheless, the current evidence is limited by small sample sizes, short follow-up, and inconsistent methodologies. Future large-scale, standardized clinical trials are required to validate MSC-based regenerative therapies and optimize treatment protocols. Full article

Background: Bone marrow mesenchymal stem cells (BM-MSCs) are significant in chemo- and radiotherapy resistance. Previous research has focused on BM-MSCs, demonstrating their functional involvement in cancer progression as mediators in the tumor microenvironment. They play multiple roles in tumorigenesis, angiogenesis, and metastasis. BM-MSC-derived exosomes (BM-MSCs-exo) are small vesicles, typically 50–300 nm in diameter, isolated from BM-MSCs. Some studies have demonstrated the tumor-suppressive effects of BM-MSCs-exo. Objective: This study aimed to investigate their role in modulating the impact of chemoradiotherapy (CRT) in different types of cervical cancer spheroid cells. Methods: The spheroids after treatment were subject to size measurement, cell viability, and caspase activity. Then, the molecular mechanism was elucidated by Western blot analysis. Results: We observed a reduction in spheroid size and an increase in cell death in HeLa spheroids, while no significant changes in size or cell viability were found in SiHa spheroids. At the molecular level, CRT treatment combined with BM-MSCs-exo in HeLa spheroids induced apoptosis through the activation of the NF-κB pathway, specifically via the NF-κB1 (P50) transcription factor, leading to the upregulation of apoptosis-related molecules. In contrast, CRT combined with BM-MSCs-exo in SiHa spheroids exhibited an opposing effect: although cellular viability decreased, caspase activity also decreased, which correlated with increased HSP27 expression and the subsequent downregulation of apoptotic molecules. Conclusion: Our study provides deeper insight into the potential of BM-MSCs-exo in cervical cancer treatment, supporting the development of more effective and safer therapeutic strategies for clinical application. Full article

The rabbit is a widely used experimental model for human translational research and stem cell therapy. Many studies have focused on rabbit mesenchymal stem cells from different biological sources for their possible application in regenerative medicine. However, a minimal number of studies have been published aimed at rabbit hematopoietic stem/progenitor cells, mainly due to the lack of specific anti-rabbit CD34 antibodies. In general, CD34 antigen is commonly used to identify and isolate hematopoietic stem/progenitor cells in humans and other animal species. The aim of this study was to develop novel monoclonal antibodies highly specific to rabbit CD34 antigen. We used hybridoma technology, two synthetic peptides derived from predicted rabbit CD34 protein, and a recombinant rabbit CD34 protein as immunogens to produce monoclonal antibodies (mAbs) specific to rabbit CD34. The produced antibodies were screened for their binding activity and specificity using ELISA, flow cytometry, and Western blot analysis. Finally, four mAbs (58/47/26, 58/47/34, 182/7/80, and 575/36/8) were selected for the final purification process. The purified mAbs recognized up to 2–3% of total rabbit bone marrow cells, while about 2% of those cells exhibited CD45 expression, which are likely rabbit primitive hematopoietic stem cells and their hematopoietic progenitors, respectively. The newly generated and purified mAbs specifically recognize CD34 antigen in rabbit bone marrow or peripheral blood and can be therefore used for further immunological applications, to study rabbit hematopoiesis or to establish a new animal model for hematopoietic stem cell transplantation studies. Full article

Research in the field of stem cells in necrotizing enterocolitis has primarily focused on the curative role of specific cells—mostly bone marrow and amniotic fluid stem cells. The impact of stem cells on reducing inflammatory cytokine levels in the necrotizing enterocolitis (NEC) model has been studied in accordance with the effects they pose on histopathology. Taking into consideration the possible paracrine mechanism of action of stem cells, our group hypothesized that lowering the initial levels of proinflammatory cytokines may be one of the mechanisms affecting the clinical outcome. A self-modified rat NEC model was used to show the effect of intraperitoneal administration of adipose derived stem cells on the initial levels of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alfa) in comparison with the interleukin levels in NEC animals and control animals without adipose–derived stem cells (ADSCs) injection. We showed a statistically significant difference in the levels of interleukins when comparing an ADSC injected group and an NEC group. This suggests that one of the mechanisms in which stem cells impact the clinical outcomes in NEC may be by alleviating the initial levels of proinflammatory cytokines. Full article

Mesenchymal stem cells (MSCs) represent a promising cell source for cartilage tissue engineering due to their chondrogenic potential. However, current differentiation protocols result in limited efficiency. This study assessed the combined effects of transforming growth factor-beta 3 (TGF-β3) and fibroblast growth factor-2 (FGF-2) on the morphology, proliferation, chondrogenic differentiation, chondrogenic gene expression, and cytokine profile of ovine bone marrow-derived MSCs (BM-MSCs). BM-MSCs were cultured under four conditions: control (αMEM) or αMEM supplemented with FGF-2, TGF-β3, or TGF-β3 + FGF-2. Morphological and proliferation analyses, Alcian blue staining in 2D and 3D, and real-time PCR for early (Chad, Comp, and Sox 5) and late (Agg, Col IX, Sox 9, and Fmod) chondrogenic markers were performed. Cytokine secretion profiles were analyzed using multiplex assay. TGF-β3 induced morphological changes indicative of early chondrogenesis, while FGF-2 enhanced proliferation. The combination of both cytokines led to a synergistic increase in cell proliferation, early and late chondrogenic gene expression, and glycosaminoglycans (GAG) deposition. Cytokine analysis revealed that TGF-β3 enhanced the immunomodulatory and angiogenic profile of BM-MSCs, whereas co-treatment with FGF-2 yielded a balanced and potentially regenerative secretome. Dual stimulation with TGF-β3 and FGF-2 significantly improves the chondrogenic differentiation of ovine BM-MSCs by enhancing both molecular and functional markers of cartilage formation. Full article

Mesenchymal stem cells (MSCs) have recently shown great promise as potential anticancer drug delivery carriers. MSCs exhibit tropism to inflammatory sites, such as tumor beds, and resistance to chemotherapeutics. The aim of this study was to examine the efficacy of gemcitabine (GEM) conjugated with flurbiprofen (FLU) as a potential agent enhancing the GEM cytotoxic effect. Pancreatic cancer cell lines (PCCs), including PANC-1, AsPC-1, and BxPC-3, were studied meticulously. Moreover, the usefulness of bone-marrow-derived mesenchymal stem cells (BM-MSCs) treated with GEM and FLU, and the conditioned media from above these cells (CM) as elements supporting the in vitro action of GEM, inducing apoptosis, necrosis, and inhibiting the cell cycle, was tested. The results showed that CM-GEM exhibited higher cytotoxicity towards the selected PCCs compared to GEM alone. Furthermore, the obtained data revealed lower sensitivity of these cells to treatment, which promotes the utilization of BM-MSCs as potential drug carriers. Based on the presented findings, it seems that applying FLU in the antiproliferative effect of GEM might be regarded as an effective strategy in the therapy of pancreatic cancer, especially in the inhibition of proliferation and induction of cancer cell death. Full article

Mesenchymal stem cells (MSCs) have a broad clinical potential, but their selection and expansion on plastic cause unknown purity and phenotypic alterations, reducing therapy efficiency. Furthermore, their behavior in non-adherent conditions during systemic transplantation remains poorly understood. The sphere formation from single cells is commonly used to assess stemness, but MSCs lack this ability, raising questions about their anchorage dependence for proliferation. We investigated whether bone marrow-derived MSCs can complete cytokinesis in non-adherent environments. Primary human and mouse bone marrow-derived MSCs were synchronized in early mitosis using nocodazole and were cultured on soft, rigid, or non-adherent surfaces. Both human and mouse MSCs displayed an ALIX (abscission licensor) recruitment to the midbody 40–90 min post-nocodazole release, regardless of the substrate adherence. Cells maintained for 4hr in the suspension remained viable, and daughter cells rapidly migrated apart upon the re-adhesion to fibronectin-coated surfaces, demonstrating cytokinesis completion in suspension. These findings distinguish MSCs from fibroblasts (which require adhesion for division), provide a more general stemness feature, and suggest that adhesion-independent cytokinesis is a trait relevant to the post-transplantation survival and tissue homing. This property may offer strategies to expand MSCs with an improved purity and functionality and to enhance engraftment by leveraging cell cycle manipulation to promote an early extracellular matrix deposition at target sites. Full article

Nanotechnology is transforming contemporary medicine by providing cutting-edge tools for the treatment and diagnosis of complex disorders. Advanced techniques such as bioimaging and photodynamic therapy (PDT) combine early diagnosis and targeted therapy, offering a more precise approach than conventional treatments. However, a significant obstacle for PDT is the need to selectively deliver photosensitizers to disease sites while minimizing systemic side effects. In this context, mesenchymal stem cells have emerged as promising biological carriers due to their natural tropism towards tumors, low immunogenicity, and their ability to overcome biological barriers. In this study, two push–pull compounds, NPI-PTZ and BTZ-PTZ, phenothiazine derivatives featuring aggregation-induced emission (AIE) abilities, were analyzed. These molecules proved to be excellent fluorescent probes and photosensitizing agents. When administered to human bone marrow-derived multipotent stromal cells (hBM-MSCs) and human adipose multipotent stem cells (hASCs), the compounds were efficiently internalized, maintained a stable fluorescent emission for several days, and showed phototoxicity after irradiation, without inducing major cytotoxic effects under normal conditions. These results highlight the potential of NPI-PTZ and BTZ-PTZ combined with mesenchymal stem cells as theranostic tools, bridging bioimaging and PDT, and suggest new possibilities for advanced therapeutic approaches in clinical applications. Full article

Osteoarthritis (OA) is a prevalent and debilitating joint disorder that affects a substantial proportion of the global population, underscoring the urgent need for therapeutic strategies that extend beyond symptomatic management. Although mesenchymal stem cells (MSCs) have emerged as a promising therapeutic modality, their clinical application remains constrained by several inherent limitations. This study explores a cell-free alternative by investigating the therapeutic potential of exosomes derived from bone marrow (BMSCs), adipose tissue (ADSCs), and umbilical cord (UMSCs) MSCs in mitigating OA pathogenesis, utilizing both in vitro and ex vivo models. Exosomes from each MSC source were isolated and characterized through nanoparticle tracking analysis, transmission electron microscopy, and Western blotting to confirm their identity and purity. Subsequently, their chondroprotective, anti-inflammatory, and regenerative properties were systematically assessed through evaluations of cell viability, expression profiles of inflammatory and chondroprotective markers, and chondrocyte migration assays. The results demonstrate that all three types of MSC-derived exosomes (MSC-Exos) exhibit low cytotoxicity while significantly suppressing proinflammatory markers and enhancing the expression of chondroprotective genes. Notably, BMSC-Exos and UMSC-Exos displayed superior efficacy in attenuating inflammation, promoting cartilage protection, and inhibiting chondrocyte apoptosis. Furthermore, all MSC-Exos markedly enhanced chondrocyte motility, a critical component of cartilage repair. Collectively, these findings support the therapeutic promise of MSC-Exos, particularly those derived from BMSCs and UMSCs, as a targeted, cell-free approach for the treatment of OA compared to ADSCs. By modulating inflammation, promoting cartilage regeneration, and preventing chondrocyte apoptosis, MSC-Exos may serve as a viable and scalable alternative to current MSC-based therapies for this widespread degenerative disease. Full article

Aging disrupts the bone marrow (BM) niche, a complex microenvironment crucial for hematopoietic stem cell (HSC) maintenance. A key, yet debated, hallmark of this aging process is the accumulation of bone marrow adipocytes (BMAds). This review explores the evolving role of BMAds in the aging BM, particularly their influence on HSC regulation via metabolic, endocrine, and inflammatory pathways. Aging BMAds exhibit altered secretory profiles, including reduced leptin and adiponectin and increased pro-inflammatory signals, which skew hematopoiesis toward myeloid over lymphoid lineage production. Additionally, shifts in fatty acid composition and lactate signaling from BMAds may impair stem cell function. These changes, alongside aging-associated alterations in vascular, neural, and stromal components of the niche, contribute to diminished immune resilience in older adults. We discuss emerging therapeutic strategies targeting BMAd-derived factors, such as DPP4 inhibition or the modulation of β-adrenergic signaling, aimed at creating a more youthful BM environment. By summarizing current insights into the aging BM niche and the central role of BMAds, this review highlights mechanisms that could be targeted to rejuvenate hematopoiesis and improve immune function in the elderly. Full article

Biomaterials play a crucial role in the long-term success of bone implant treatment. The accumulation of bacterial biofilm on the implants induces inflammation, leading to implant failure. Modification of the implant surface with bioactive molecules is one of the strategies to improve biomaterial compatibility and limit inflammation. In this study, whey protein isolate (WPI) fibrillar coatings were used as a matrix to incorporate biologically active phenolic compound phloroglucinol (PG) at different concentrations (0.1% and 0.5%) on titanium alloy (Ti6Al4V) scaffolds. Successful Ti6Al4V coatings were validated by X-ray photoelectron spectroscopy (XPS), showing a decrease in %Ti and increases in %C, %N, and %O, which demonstrate the presence of the protein layer. The biological activity of PG-enriched WPI (WPI/PG) coatings was assessed using bone-forming cells, human bone marrow-derived mesenchymal stem cells (BM-MSCs). WPI/PG coatings modulated the behavior of BM-MSCs but did not have a negative impact on cell viability. A WPI with higher concentrations of PG increased gene expression relative to osteogenesis and reduced the pro-inflammatory response of BM-MSCs after biofilm stimulation. Autoclaving reduced WPI/PG bioactivity compared to filtration. By using WPI/PG coatings, this study addresses the challenge of improving osteogenic potential while limiting biofilm-induced inflammation at the Ti6Al4V surface. These coatings represent a promising strategy to enhance implant bioactivity. Full article

Aim: This systematic review aims to evaluate the use of mesenchymal stem cells, particularly those derived from bone marrow, adipose tissue, and dental pulp in maxillofacial and oral surgery, focusing on their regenerative potential, clinical applications, and integration with biomaterials. Introduction: Mesenchymal stem cells are multipotent stem cells known for their immunomodulatory and regenerative abilities. Their low immunogenicity and differentiation capacity make them ideal for treating craniofacial defects and enhancing soft tissue repair. Materials and Methods: The review followed PRISMA guidelines and was registered in PROSPERO. The literature was searched across PubMed, Scopus, and Web of Science from 2009 to 2024. Twelve studies met the inclusion criteria and were analyzed for clinical efficacy and methodological quality. Results: Clinical trials demonstrated the safety and regenerative benefits of mesenchymal stem cell in bone and soft tissue reconstruction. Adipose-derived stem cell and dental pulp stem cell showed favorable outcomes in angiogenesis and healing, while bone marrow’s cell proved effective in bone regeneration, particularly when combined with scaffolds. Discussion and Conclusions: Although results are promising, limitations remain in consistency and long-term outcomes. Optimizing scaffold integration, preservation methods, and delivery techniques is crucial. Mesenchymal stem cell-based therapies represent a powerful, minimally invasive alternative to traditional grafting in oral and maxillofacial surgery. Full article

Background/Objectives: Acute leukemia (AL) alters both hematopoiesis and the bone marrow stromal microenvironment. Attempts to develop a culture of multipotent mesenchymal stromal cells (MSCs) from AL patients’ bone marrow are not always successful, as opposed to healthy donors’ bone marrow. Methods: To unveil the reason, healthy donors’ MSCs were cultured in the presence of sera from healthy donors (control group) or AL patients at the onset of the disease, in short- and long-term remission, and before and after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Results: The cell yield in the presence of patient sera was lower than in the control, regardless of the AL stage. It was assumed that the patients either lacked growth factors to sustain MSCs, or there were inhibitors of MSC growth present. The serum’s ability to support MSC growth correlated with platelet count and albumin and calcium concentrations in patients’ blood. Platelet-derived growth factors—PDGFA and PDGFB—are known to induce MSC growth. Their concentration in the serum of AL patients and healthy donors was analyzed. A decrease in PDGFA concentration was found in the sera of patients compared to healthy donors. PDGFB concentration was lower at disease onset, increased during remission and decreased again during relapse. PDGFB concentration correlated with platelet count, while PDGFA concentration did not. AL patients’ sera reflected systemic disturbances affecting MSC growth. So far, decreases in PDGFs, albumin and calcium concentration, as well as platelet count, are the parameters that might be among the causes of this observation. Full article

Acute radiation syndrome (ARS) results from high-dose ionizing radiation (IR) exposure, with bone marrow (BM) being highly susceptible due to its proliferative activity. BM injury causes pancytopenia, leading to infections, anemia, and bleeding. Mesenchymal stem cells (MSCs) hold promise for ARS treatment because of their immunomodulatory, anti-inflammatory, and regenerative properties. However, challenges such as replicative senescence, poor survival, and engraftment in irradiated microenvironments limit their efficacy. This study evaluated rapamycin-preconditioned placenta-derived MSCs (rPD-MSCs) in a mouse ARS model. Rapamycin was selected for preconditioning due to its ability to induce autophagy and modulate cytokine secretion. We assessed rapamycin-dependent modulation of autophagy-related genes and proteins, as well as hematopoietic cytokines secretion in PD-MSCs, and evaluated morphological changes in blood and BM at 7 and 21 days post-irradiation in ICR/CD1 mice. Preconditioning with rapamycin alters the secretion of granulocyte colony-stimulating factor (G-CSF), stem cell factor (SCF), and Fms-related tyrosine kinase 3 ligand (Flt3LG) in PD-MSCs without affecting cell viability. rPD-MSCs better enhance hematopoietic recovery, restore bone marrow cellularity, and increase peripheral blood cell counts by elevating the secretion of hematopoietic cytokines compared to non-preconditioned cells. These results highlight rapamycin preconditioning as a promising strategy to enhance MSCs therapeutic potential for ARS, supporting further preclinical and clinical exploration. Full article

Objectives: Traditional 2D cell cultures on flat surfaces fail to replicate 3D environments, affecting cellular morphology and function. Various 3D techniques (e.g., spheroids, organoids, organs-on-chips, 3D bioprinting) have been used for disease modelling and drug testing, but their application in hard tissues remains challenging. This study aimed to develop a biocompatible 3D culture method for bone tissue organoids using human bone marrow-derived stem cells (hBMSCs) and hydrogels. Methods: hBMSCs were isolated from human jawbone marrow. The control group was cultured under 2D conditions, whereas the experimental group was cultured in a 3D hydrogel environment. In vitro analyses, including flow cytometry and RNA sequencing, were performed. Quantitative data were statistically analysed at a 0.05 level of significance. Results: hBMSCs cultured in 3D hydrogel conditions indicated enhanced reproducibility, increased cell viability, and significant osteogenic differentiation. Genes such as MMP-13, LPL, and SP7 showed substantially higher expression in 3D cultures, with protein-level confirmation by Western blot. These findings suggest that 3D culture more effectively supports the natural growth and differentiation of hBMSCs. Conclusions: Culturing hBMSCs in a 3D environment more closely mimics in vivo conditions, thus promoting the expression and activity of critical proteins involved in hBMSC differentiation. Full article