PubMed İndeksli Yayınlar Koleksiyonu
Permanent URI for this collectionhttps://hdl.handle.net/20.500.12573/397
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Article Unveiling the Therapeutic Role of 3D-Cultured Mesenchymal Stem Cells in Diabetic Foot Ulcers through Transcriptomic Integration and Fibroblast Modulation(Springer, 2026-03-31) Ozturk, Esengul; Bicer, MesudeBackground Diabetic foot ulcers (DFUs) are among the most severe complications of diabetes mellitus and remain difficult to manage due to chronic inflammation, defective angiogenesis, delayed tissue repair, which increase the risk of recurrence and limb amputation. Standard treatments, such as debridement, infection management, pressure off-loading and revascularization, are commonly used, however; these interventions often inadequate to fully restore effective wound repair. Mesenchymal stem cells (MSCs) have attracted remarkable interest due to their potential regenerative ability and paracrine activity. Nevertheless, the molecular interaction between MSCs and fibroblasts under hyperglycemic conditions has not been fully elucidated. Objective This study aimed to examine differentially expressed genes (DEGs) associated with DFUs and MSC-related regenerative mechanisms using transcriptomic datasets (such as GSE143735, GSE199939, and GSE217709). Methods and results Differentially expressed genes and protein-protein interaction (PPI) network analysis were performed to determine central regulatory genes. Four key genes including CXCL1, MMP9, THBS1, and POSTN were recognized as hub genes related to inflammatory response, extracellular matrix reorganization, and angiogenesis. For experimental validation, L929 murine fibroblasts were exposed to high-glucose conditions to set-up an in vitro diabetic model and subsequently treated with MSCs with/without a 3D platform. Hyperglycemic conditions significantly reduced fibroblast proliferation and migration downregulated the expression of the identified hub genes and enhanced apoptotic activity. MSC treatment partially increased cellular function, while MSCs embedded into 3D culture enhanced a more pronounced recovery in both gene expression patterns and functional assays. Conclusions These findings suggest that high glucose impair fibroblast functions for wound repair, while 3D-cultured MSCs enhance regenerative responses and may represent a promising strategy for diabetic wound healing.Article Citation - WoS: 2Citation - Scopus: 2Antifungal Efficacy of 3D-Cultured Palatal Mesenchymal Stem Cells and Their Secreted Factors Against Candida albicans(American Chemical Society, 2025-09-19) Bicer, M.; Öztürk, E.; Sener, F.; Hakki, S.S.; Fidan, O.Candida albicans is among the life-threatening fungal species and the primary contributor to hospital-acquired systemic infections, accounting for nearly 70% of all fungal infections worldwide. The current treatment primarily relies on azoles, pyrimidine analogs, polyenes, and echinocandins. However, growing antifungal resistance highlights the urgent need for the development of alternative treatments against C. albicans. Mesenchymal stem cells (MSCs) offer huge therapeutic potential for the treatment of C. albicans-associated diseases. In this study, palatal adipose tissue-derived MSCs (PAT-MSCs) and PAT-MSCs cultured in 3D biomaterial using nanofibrillar cellulose were tested against C. albicans strains ATCC 10231 and ATCC MYA 2876 using an in vitro antifungal activity assay. In addition, the conditioned medium from both PAT-MSCs and PAT-MSCs cultured in 3D hydrogel biomaterial (CM-PAT-MSCs-3D) were evaluated for their antifungal activities. The combined effect of PAT-MSCs and their secreted factors was also investigated. The expression of five antimicrobial peptide (AMP)-encoding genes was analyzed by quantitative real-time PCR. The expression of antimicrobial peptides was further confirmed via immunocytochemical staining. PAT-MSCs significantly inhibited the growth of C. albicans strains at varying inoculum concentrations (500 and 2000 CFU). Similarly, a comparable antifungal effect was observed when Candida strains were treated with PAT-MSC secreted factors alone. Statistical analysis revealed significant differences between the antifungal activities of PAT-MSCs and CM-PAT-MSCs. Lastly, the combination of PAT-MSCs and CM-PAT-MSC-3D led to a marked reduction in fungal growth, with inhibition rates of 99.75% and 99.91% for C. albicans ATCC 10231 and ATCC MYA-2876, respectively, at 500 CFU inocula. At 2000 CFU inocula, inhibition rates were 99.54% and 99.91%, respectively (****P ≤ 0.0001). These antifungal activities were further confirmed by using RT-PCR and immunocytochemical analysis. Our findings underscore a perspective on the potent antifungal activity of secreted factors from PAT-MSCs cultured within a 3D hydrogel matrix, specifically against various strains of C. albicans. Particularly, the combination of PAT-MSCs with their secreted factors represents a promising therapeutic platform, potentially offering a safer and more effective alternative to conventional antifungal treatments. © 2025 Elsevier B.V., All rights reserved.