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.Article Citation - WoS: 10Citation - Scopus: 11Time-Dependent Reduction of Calcium Oscillations in Adipose-Derived Stem Cells Differentiating Towards Adipogenic and Osteogenic Lineage(MDPI, 2021-09-23) Torre, Enrico C.; Bicer, Mesude; Cottrell, Graeme S.; Widera, Darius; Tamagnini, FrancescoAdipose-derived mesenchymal stromal cells (ASCs) are multipotent stem cells which can differentiate into various cell types, including osteocytes and adipocytes. Due to their ease of harvesting, multipotency, and low tumorigenicity, they are a prime candidate for the development of novel interventional approaches in regenerative medicine. ASCs exhibit slow, spontaneous Ca2+ oscillations and the manipulation of Ca2+ signalling via electrical stimulation was proposed as a potential route for promoting their differentiation in vivo. However, the effects of differentiation-inducing treatments on spontaneous Ca2+ oscillations in ASCs are not yet fully characterised. In this study, we used 2-photon live Ca2+ imaging to assess the fraction of cells showing spontaneous oscillations and the frequency of the oscillation (measured as interpeak interval-IPI) in ASCs undergoing osteogenic or adipogenic differentiation, using undifferentiated ASCs as controls. The measurements were carried out at 7, 14, and 21 days in vitro (DIV) to assess the effect of time in culture on Ca2+ dynamics. We observed that both time and differentiation treatment are important factors associated with a reduced fraction of cells showing Ca2+ oscillations, paralleled by increased IPI times, in comparison with untreated ASCs. Both adipogenic and osteogenic differentiation resulted in a reduction in Ca2+ dynamics, such as the fraction of cells showing intracellular Ca2+ oscillations and their frequency. Adipogenic differentiation was associated with a more pronounced reduction of Ca2+ dynamics compared to cells differentiating towards the osteogenic fate. Changes in Ca2+ associated oscillations with a specific treatment had already occurred at 7 DIV. Finally, we observed a reduction in Ca2+ dynamics over time in untreated ASCs. These data suggest that adipogenic and osteogenic differentiation cell fates are associated with specific changes in spontaneous Ca2+ dynamics over time. While this observation is interesting and provides useful information to understand the functional correlates of stem cell differentiation, further studies are required to clarify the molecular and mechanistic correlates of these changes. This will allow us to better understand the causal relationship between Ca2+ dynamics and differentiation, potentially leading to the development of novel, more effective interventions for both bone regeneration and control of adipose growth.Article Citation - WoS: 8Citation - Scopus: 11Stem Cells Combined 3D Electrospun Nanofibrous and Macrochannelled Matrices: A Preliminary Approach in Repair of Rat Cranial Bones(Taylor & Francis Ltd, 2019-04-03) Isoglu, Ismail Alper; Bolgen, Nimet; Korkusuz, Petek; Vargel, Ibrahim; Celik, Hakan Hamdi; Kilic, Emine; Piskin, ErhanRepair of cranial bone defects is an important problem in the clinical area. The use of scaffolds combined with stem cells has become a focus in the reconstruction of critical-sized bone defects. Electrospinning became a very attracting method in the preparation of tissue engineering scaffolds in the last decade, due to the unique nanofibrous structure of the electrospun matrices. However, they have a limitation for three dimensional (3D) applications, due to their two-dimensional structure and pore size which is smaller than a cellular diameter which cannot allow cell migration within the structure. In this study, electrospun poly(epsilon-caprolactone) (PCL) membranes were spirally wounded to prepare 3D matrices composed of nanofibers and macrochannels. Mesenchymal stromal/stem cells were injected inside the scaffolds after the constructs were implanted in the cranial bone defects in rats. New bone formation, vascularisation and intramembranous ossification of the critical size calvarial defect were accelerated by using mesenchymal stem cells combined 3D spiral-wounded electrospun matrices.Article Citation - WoS: 28Citation - Scopus: 31Proteomic and Biological Analysis of the Effects of Metformin Senomorphics on the Mesenchymal Stromal Cells(Frontiers Media S.A., 2021-10-05) Acar, Mustafa Burak; Ayaz-Guner, Serife; Gunaydin, Zeynep; Karakukcu, Musa; Peluso, Gianfranco; Di Bernardo, Giovanni; Galderisi, UmbertoSenotherapeutics are new drugs that can modulate senescence phenomena within tissues and reduce the onset of age-related pathologies. Senotherapeutics are divided into senolytics and senomorphics. The senolytics selectively kill senescent cells, while the senomorphics delay or block the onset of senescence. Metformin has been used to treat diabetes for several decades. Recently, it has been proposed that metformin may have anti-aging properties as it prevents DNA damage and inflammation. We evaluated the senomorphic effect of 6 weeks of therapeutic metformin treatment on the biology of human adipose mesenchymal stromal cells (MSCs). The study was combined with a proteome analysis of changes occurring in MSCs' intracellular and secretome protein composition in order to identify molecular pathways associated with the observed biological phenomena. The metformin reduced the replicative senescence and cell death phenomena associated with prolonged in vitro cultivation. The continuous metformin supplementation delayed and/or reduced the impairment of MSC functions as evidenced by the presence of three specific pathways in metformin-treated samples: 1) the alpha-adrenergic signaling, which contributes to regulation of MSCs physiological secretory activity, 2) the signaling pathway associated with MSCs detoxification activity, and 3) the aspartate degradation pathway for optimal energy production. The senomorphic function of metformin seemed related to its reactive oxygen species (ROS) scavenging activity. In metformin-treated samples, the CEBPA, TP53 and USF1 transcription factors appeared to be involved in the regulation of several factors (SOD1, SOD2, CAT, GLRX, GSTP1) blocking ROS.Article Citation - WoS: 17Citation - Scopus: 18Obesity Induced by High-Fat Diet Is Associated With Critical Changes in Biological and Molecular Functions of Mesenchymal Stromal Cells Present in Visceral Adipose Tissue(Impact Journals LLC, 2020-12-27) Acar, Mustafa Burak; Ayaz-Guner, Serife; Di Bernardo, Giovanni D.; Guner, Hüseyin; Murat, Ayşegül; Peluso, G. F.; Galderisi, UmbertoThe mesenchymal stromal cells (MSCs) residing within the stromal component of visceral adipose tissue appear to be greatly affected by obesity, with impairment of their functions and presence of senescence. To gain further insight into these phenomena, we analyzed the changes in total proteome content and secretome of mouse MSCs after a high-fat diet (HFD) treatment compared to a normal diet (ND). In healthy conditions, MSCs are endowed with functions mainly devoted to vesicle trafficking. These cells have an immunoregulatory role, affecting leukocyte activation and migration, acute inflammation phase response, chemokine signaling, and platelet activities. They also present a robust response to stress. We identified four signaling pathways (TGF-β, VEGFR2, HMGB1, and Leptin) that appear to govern the cells’ functions. In the obese mice, MSCs showed a change in their functions. The immunoregulation shifted toward pro-inflammatory tasks with the activation of interleukin-1 pathway and of Granzyme A signaling. Moreover, the methionine degradation pathway and the processing of capped intronless pre-mRNAs may be related to the inflammation process. The signaling pathways we identified in ND MSCs were replaced by MET, WNT, and FGFR2 signal transduction, which may play a role in promoting inflammation, cancer, and aging © 2024 Elsevier B.V., All rights reserved.