Introduction:Liver diseases remain a major global health burden, with limited treatment options for advanced hepatic dysfunction. Current treatment options are limited and mainly supportive, with liver transplantation being the only definitive therapy in advanced cases. Stem cell-based therapies have emerged as a promising alternative due to their regenerative and immunomodulatory properties. Stem cells can differentiate and produce identical daughter cells. Umbilical cord-derived mesenchymal stem cells (UC-MSCs) hold promise for liver regeneration but show limited hepatic differentiation efficiency. Preconditioning with FGF and IGF may enhance their differentiation, survival, and functional potential. This study aims to investigate the effect of FGF and IGF pre-treatment on the differentiation capacity of UC-MSCs and their potential application in regenerative therapy for liver fibrosis or cirrhosis. Methods:Cell viability was evaluated through MTT, crystal violet, and trypan blue assays. For the assessment of differentiation potential, ELISA and Immunocytochemistry of HNF4α and ASGPR1 were performed, for angiogenesis and apoptosis, ELISA of VEGF and p53 were performed. Furthermore, antioxidant enzyme activity was also assessed. Results:UC-MSCs preconditioned with FGF and IGF exhibited significantly enhanced viability and reduced cell death, as confirmed by MTT, crystal violet, trypan blue assays, and ELISA of VEGF and P53. ELISA and immunocytochemistry of HNF4α and ASGPR1 demonstrated marked upregulation of these hepatic markers in the preconditioned groups. The gene expression analysis confirmed superior regenerative potential in the FGF+IGF-treated group. Antioxidative analysis further validated a higher level of antioxidative potential in preconditioned cells. Conclusion:Preconditioned UC-MSCs offer a promising cellbased alternative to liver transplantation by enhancing regeneration, reducing apoptosis, promoting angiogenesis and increasing antioxidant defense in damaged liver tissue.
Background: Atypical femoral fractures (AFFs) are rare complications often linked to prolonged bisphosphonate use. This pilot study evaluated the feasibility of intraoperative intramedullary photobiomodulation therapy (PBMT) using long, sterile optical fibers during surgical fixation. Methods: Eleven elderly female patients with AFFs were randomized into a PBMT-treated group or control. PBMT was applied using a red laser (638 nm, 3.2 J per point). Results: No statistically significant differences in healing, complications, or function were observed. However, a trend toward improved RUSTm scores in the PBMT group emerged. Conclusion: This novel technique appears feasible and safe; further studies are needed to assess its regenerative potential
Introduction:Impaired proliferation and differentiation capacity of adipose-derived mesenchymal stem cells (AD-MSCs) in obesity hinder the formation of metabolically healthy adipocytes, thereby aggravating metabolic disorders. Photobiomodulation (PBM) is a simple, non-invasive light-based therapy that primarily uses red and near-infrared light and has been shown to enhance the proliferation and differentiation potential of stem cells, including AD-MSCs. However, the wide variation in PBM parameters used in previous studies necessitates further investigation to determine optimal dosage and delivery methods. This study aimed to construct a simple, easy-to-assemble LED panel for PBM application and to identify an effective dose that stimulates proliferation and adipogenic differentiation of AD-MSCs. Methods:The panel delivered 1 J/cm2 of 660 nm red light, either daily (P1Pro and P1Diff group) or every other day (P2Pro and P2Diff group). Results:No significant differences in total cell count or viability were observed among the groups, indicating that the PBM protocol is safe. KI-67 expression was similar between the P1Pro and control groups (Control: 1.00 ± 0.02; P1Pro: 1.19 ± 0.06, p > 0.05), whereas the P2Pro group showed a significant decrease compared with P1Pro (P2Pro: 0.71 ± 0.06, p = 0.02). The P1Diff group also exhibited a significant increase in expression of adipogenic markers PPARꙋ and CEBPα (1.55 ± 0.04, p < 0.01 and 2.9 ± 0.3, p < 0.01, respectively), while the P2Diff group showed minimal to no difference compared with the control. Conclusion:Although further studies are required to assess PBM effects on dysfunctional AD-MSCs from obese individuals, this study demonstrates that a simple, easy-to-assemble PBM device can safely and effectively enhance the proliferation and differentiation capacity of AD-MSCs.
Objective:This study aims to investigate the role of exosomes derived from bone marrow mesenchymal stem cell (BMSC) with or without hypoxic precondition (HP) play in ischemic stroke, and the underlying mechanisms. Methods:Exosomes were characterized by transmission electron microscopy, western blot, and nanoparticle tracking analysis. To simulate neuronal ischemia-reperfusion injury, PC-12 cells underwent oxygen-glucose deprivation followed by reoxygenation (OGD/R). Cell viability and membrane integrity were assessed using CCK-8 and LDH assays, respectively. Apoptosis was evaluated by flow cytometry and TUNEL assay, while the expression of apoptosis-related proteins was analyzed via western blot. Results:Exosomes derived from BMSC activated the PI3K/Akt signaling pathway and subsequently suppressed apoptosis, thereby ameliorating cellular injury induced by OGD/R. HP enhanced exosome secretion from BMSC; however, it did not significantly alter the particle size distribution of the released exosomes. Notably, when administered at the same concentration, no substantial difference in therapeutic efficacy was observed between exosomes derived from normoxic BMSC and those from HP-treated BMSC. The anti-apoptotic effects conferred by these exosomes were effectively abolished upon treatment with the PI3K inhibitor LY294002, indicating a PI3K/Akt-dependent mechanism. Conclusions:Exosomes derived frvom BMSC effectively inhibitedp aupoptposis induced by OpGD/R through uactivation of the PI3K/Akt. Although HP significantly enhanced the secretion of exosomes from BMSC, it did not improve the therapeutic efficacy of these exosomes when administered at an equivalent dosage.
Articular cartilage has limited self-repair ability, making osteoarthritis a major challenge due to aging and mechanical stress. While current therapies provide partial functional improvement, their outcomes remain suboptimal, highlighting the need for regenerative strategies. Mesenchymal stem cells (MSCs) show promises due to their chondrogenic potential, and kartogenin (KGN) enhances this process. This study examines KGN-loaded gelatin microspheres (KMs) for cartilage regeneration. KMs were synthesized via gelatin-KGN dispersion in ice-cooled hexane, followed by glutaraldehyde cross-linking. Scanning electron microscopy showed porous KMs (200-800 μm) with interconnected pores (2-10 μm), while Fourier transform infrared spectroscopy confirmed gelatin and KGN presence. hMSCs were cultured with KMs, showing no cytotoxicity. Gene expression analysis revealed upregulated chondrogenic markers (SOX9, ACAN, COMP, COL2A1). Western blotting and immunofluorescence confirmed increased chondrogenic protein production. Sulfated glycosaminoglycan content increased over four weeks, indicating extracellular matrix maturation. This study demonstrates that KMs effectively deliver KGN, enhancing MSC chondrogenesis. Small molecule-based biomaterials may offer an alternative to growth factors in osteochondral tissue engineering, warranting further in vivo validation.
Introduction:Ureteral injuries can lead to renal dysfunction, and conventional treatments such as ureteral stents and autologous tissue grafts have limitations. This study aimed to evaluate the biocompatibility of a "biotube" created using in-body tissue architecture (iBTA) technology for ureteral reconstruction in a canine model. Methods:Biotubes were implanted in dogs to replace a segment of the ureter. Ureteral stents were used to prevent obstruction. Autopsies were performed 2-3 months after implantation, and the implantation sites were examined histologically to assess tissue regeneration, vascularization, and potential inflammatory reactions. Results:Ureteral stenting effectively prevented obstruction and ensured adequate urinary flow during the observation period. All biotubes were significantly shortened after implantation. No signs of inflammation or foreign body reactions were recorded, indicating good biocompatibility. Although epithelial cell invasion was observed, muscle tissue migration and angiogenesis were limited. Conclusions:Biotubes demonstrate potential as temporary ureteral substitutes; however, improvements in epithelialization and muscle tissue migration are necessary for successful long-term ureteral regeneration. Further experimental studies are required to evaluate their clinical utility as scaffold materials for ureteral reconstruction.
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.
Background:Duodenal perforation represents a critical gastrointestinal surgical emergency, often associated with high rates of morbidity and mortality. Mesenchymal stem cells (MSCs) have the potential to enhance wound healing by releasing various growth factors and antiinflammatory cytokines. This study aims to evaluate and analyze the impact of MSCs on the healing process of duodenal perforation wounds. Method:MSCs were extracted from the umbilical cords of rats and injected into the site of duodenal perforation at two different doses: 1.5 × 106 for Treatment Group 1 and 3 × 106 for Treatment Group 2. The control group consisted of rats with duodenal perforation that received local injections on normal saline. The levels of Transforming Growth Factor β (TGF-β) and Alpha Smooth Muscle Actin (α-SMA) were assessed via Western Blot analysis, while collagen and fibroblast presence were evaluated through histopathological examination. These examinations were conducted on days 3 and 7 post-treatment. Statistical analysis was performed using SPSS 25.0, with significance defined at p<0.05. Results:Significant increases in the expression of TGF-β, fibroblasts, collagen, and α-SMA were observed in the treatment groups compared to the control group on both day 3 and day 7. Conclusion:The administration of MSCs significantly enhances the proliferation phase of duodenal wound healing through the increased expression of fibroblasts, collagen, TGF-β, and α-SMA.
Objective: Mesenchymal stem cells (MSCs) suppress inflammation and promote tissue repair via paracrine factors. MSC-conditioned medium (MSC-CM), rich in these factors, shows promise as a cell-free therapy. This study explored the protein profiles of MSC-CMs from different human tissues (dental pulp, adipose tissue, umbilical cord, and placenta) to assess variations and therapeutic potential. Methods: MSCs were cultured from dental pulp, adipose tissue, umbilical cord, and placenta, and MSC-CMs were collected. Proteomic analysis using LC-MS/MS identified and quantified proteins, followed by bioinformatic analysis. Results: A total of 924 secreted proteins were identified in MSC-CMs from the four tissue sources. Extracellular matrix (ECM) signatures were prominent across all MSC-CMs. MSC-CM from adipose tissue had the highest levels of skin care-related proteins. Neuronal growthrelated proteins were most abundant in umbilical cord and placental MSC-CMs, while wound healing proteins were prominent in dental pulp Conclusions: MSC-CMs from different tissues exhibit distinct protein profiles, while sharing common ECM signatures. These findings suggest that MSC-CM could be used for specific applications such as neurodegenerative diseases and wound healing, depending on the tissue source. Further in vivo research is needed to explore their clinical relevance.
Background:Exosomes are small vesicles with intracellular origin which are released into the extracellular space. The properties of stem cell-derived exosomes are similar to their cellular origin and can be involved in repair the damaged tissues. This investigation aimed to evaluate the effect of exosomes derived from mesenchymal stem cells and cardiomyocytes on the repair of damaged cardiomyocyte in vitro. Methods:In this study, first damaged cells were created by Isopreternol treatment of mesenchymal-derived cardiomyocytes, then cells were affected by exosomes extracted from MSCs and MSC derived cardiomyocyes. Finally, mRNA levels of cardiac differentiation and damage markers were measured by Real Time PCR at the time intervals. Results:Our results showed the level of cardiac markers in damaged cardiomyocytes increased after treatment by cardiomyocytes derived exosomes compared to MSC derived exosomes. Reciprocally LDH a and b mRNA levels decrease in both conditions. Conclusion:our findings revealed the exosomes extracted from cardiomyocytes were more effective in the repair of injured cells compared to the exosomes derived MSCs.
The significant immunomodulatory capacity of mesenchymal stem cells (MSCs) is increasingly being recognized, making them valuable for the treatment of autoimmune disorders. MSCs influence immune cell behavior during therapy through intercellular communication mediated by extracellular vesicles (EVs). Moreover, MSC-derived apoptotic vesicles (apoEVs) can also exert immunomodulatory functions. This study compared the effects of dental follicle stem cells (DFSCs) and smaller apoptotic vesicles (apoSEVs) derived from DFSCs on the proliferation of peripheral blood mononuclear cells (PBMC), as well as their impact on T cell subpopulations and inflammatory factor expression. The results showed that apoSEVs derived from DFSCs significantly enhanced PBMC proliferation, inhibited Th1, Th17, and Treg cell populations, and reduced IFN-γ and TNF-α expression levels. These findings demonstrate that apoSEVsapoSEVs from DFSCs can effectively regulate immune responses in a manner similar to that of DFSCs themselves.
The proposed topic is important because it helps find a lot of problems that happen when cardiovascular diseases are passed on along with fibrosis and the link between stem cells and myocardial regeneration. This study aims to investigate the effectiveness of autologous stem cells in the treatment of post-infarction myocardial changes. Statistical, bibliographic, and bibliosemantic research methods and scientific literature for the last 6 years were used to achieve the purpose. Cardiovascular diseases hold the highest prevalence and mortality rates, second only to the number of accidents. Today, there are many methods in the fight against coronary heart disease. However, drug therapy is the least effective, and instrumental methods are too invasive and entail several complications and side effects. Therefore, conducting detailed research on the impact of stem cells on the myocardium affected by infarction presents a challenge. Stem cell transplantation, which includes autologous bone marrow stem cells, typically leads to noticeable and significant changes in cardiac hemodynamic parameters and rheological properties. The development of autologous bone marrow stem cells during the angiogenesis process substantiates such metamorphoses. In addition, factors such as vascular endothelial growth factor and the whole list of coagulogram indicators may influence these changes. The practical significance of the raised subject is using stem cell therapy as an alternative, less invasive method in the fight against postinfarction myocardial changes.
