Scopus İndeksli Yayınlar Koleksiyonu / Scopus Indexed Publications Collection
Permanent URI for this collectionhttps://hdl.handle.net/11147/7148
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Article Citation - WoS: 14Lamin A/C Is Dispensable To Mechanical Repression of Adipogenesis(MDPI, 2021) Goelzer, Matthew; Dudakovic, Amel; Olçum, Melis; Sen, Buer; Özçivici, Engin; Rubin, Janet; van Wijnen, Andre J.Mesenchymal stem cells (MSCs) maintain the musculoskeletal system by differentiating into multiple lineages, including osteoblasts and adipocytes. Mechanical signals, including strain and low-intensity vibration (LIV), are important regulators of MSC differentiation via control exerted through the cell structure. Lamin A/C is a protein vital to the nuclear architecture that supports chromatin organization and differentiation and contributes to the mechanical integrity of the nucleus. We investigated whether lamin A/C and mechanoresponsiveness are functionally coupled during adipogenesis in MSCs. siRNA depletion of lamin A/C increased the nuclear area, height, and volume and decreased the circularity and stiffness. Lamin A/C depletion significantly decreased markers of adipogenesis (adiponectin, cellular lipid content) as did LIV treatment despite depletion of lamin A/C. Phosphorylation of focal adhesions in response to mechanical challenge was also preserved during loss of lamin A/C. RNA-seq showed no major adipogenic transcriptome changes resulting from LIV treatment, suggesting that LIV regulation of adipogenesis may not occur at the transcriptional level. We observed that during both lamin A/C depletion and LIV, interferon signaling was downregulated, suggesting potentially shared regulatory mechanism elements that could regulate protein translation. We conclude that the mechanoregulation of adipogenesis and the mechanical activation of focal adhesions function independently from those of lamin A/C.Article Citation - WoS: 14Citation - Scopus: 14Development of Biological Meniscus Scaffold: Decellularization Method and Recellularization With Meniscal Cell Population Derived From Mesenchymal Stem Cells(SAGE Publications, 2021) Kara, Aylin; Koçtürk, Semra; Bilici, Gökçen; Havıtçıoğlu, HasanTissue engineering approaches which include a combination of cells and scaffold materials provide an alternative treatment for meniscus regeneration. Decellularization and recellularization techniques are potential treatment options for transplantation. Maintenance of the ultrastructure composition of the extracellular matrix and repopulation with cells are important factors in constructing a biological scaffold and eliminating immunological reactions. The aim of the study is to develop a method to obtain biological functional meniscus scaffolds for meniscus regeneration. For this purpose, meniscus tissue was decellularized by our modified method, a combination of physical, chemical, and enzymatic methods and then recellularized with a meniscal cell population composed of fibroblasts, chondrocytes and fibrochondrocytes that obtained from mesenchymal stem cells. Decellularized and recellularized meniscus scaffolds were analysed biochemically, biomechanically and histologically. Our results revealed that cellular components of the meniscus were successfully removed by preserving collagen and GAG structures without any significant loss in biomechanical properties. Recellularization results showed that the meniscal cells were localized in the empty lacuna on the decellularized meniscus, and also well distributed and proliferated consistently during the cell culture period (p < 0.05). Furthermore, a high amount of DNA, collagen, and GAG contents (p < 0.05) were obtained with the meniscal cell population in recellularized meniscus tissue. The study demonstrates that our decellularization and recellularization methods were effective to develop a biological functional meniscus scaffold and can mimic the meniscus tissue with structural and biochemical features. We predict that the obtained biological meniscus scaffolds may provide avoidance of adverse immune reactions and an appropriate microenvironment for allogeneic or xenogeneic recipients in the transplantation process. Therefore, as a promising candidate, the obtained biological meniscus scaffolds might be verified with a transplantation experiment.Article Citation - WoS: 5Citation - Scopus: 5Low Magnitude High Frequency Vibrations Expedite the Osteogenesis of Bone Marrow Stem Cells on Paper Based 3d Scaffolds(Springer, 2020) Karadaş, Özge; Meşe, Gülistan; Özçivici, EnginAnabolic effects of low magnitude high frequency (LMHF) vibrations on bone tissue were consistently shown in the literature in vivo, however in vitro efforts to elucidate underlying mechanisms are generally limited to 2D cell culture studies. Three dimensional cell culture platforms better mimic the natural microenvironment and biological processes usually differ in 3D compared to 2D culture. In this study, we used laboratory grade filter paper as a scaffold material for studying the effects of LHMF vibrations on osteogenesis of bone marrow mesenchymal stem cells in a 3D system. LMHF vibrations were applied 15 min/day at 0.1 g acceleration and 90 Hz frequency for 21 days to residing cells under quiescent and osteogenic conditions. mRNA expression analysis was performed for alkaline phosphatase (ALP) and osteocalcin (OCN) genes, Alizarin red S staining was performed for mineral nodule formation and infrared spectroscopy was performed for determination of extracellular matrix composition. The highest osteocalcin expression, mineral nodule formation and the phosphate bands arising from the inorganic phase was observed for the cells incubated in osteogenic induction medium with vibration. Our results showed that filter paper can be used as a model scaffold system for studying the effects of mechanical loads on cells, and LMHF vibrations induced the osteogenic differentiation of stem cells.Article Citation - WoS: 28Citation - Scopus: 30Bone Marrow Stem Cells Adapt To Low-Magnitude Vibrations by Altering Their Cytoskeleton During Quiescence and Osteogenesis(TUBITAK, 2015) Demiray, Levent; Özçivici, EnginApplication of mechanical vibrations is anabolic to bone tissue, not only by guiding mature bone cells to increased formation, but also by increasing the osteogenic commitment of progenitor cells. However, the sensitivity and adaptive response of bone marrow stem cells to this loading regimen has not yet been identified. In this study, we subjected mouse bone marrow stem cell line D1-ORL-UVA to daily mechanical vibrations (0.15 g, 90 Hz, 15 min/day) for 7 days, both during quiescence and osteogenic commitment, to identify corresponding ultrastructural adaptations on cellular and molecular levels. During quiescence, mechanical vibrations significantly increased total actin content and actin fiber thickness, as measured by phalloidin staining and fluorescent microscopy. Cellular height also increased, as measured by atomic force microscopy, along with the expression of focal adhesion kinase (PTK2) mRNA levels. During osteogenesis, mechanical vibrations increased the total actin content, actin fiber thickness, and cytoplasmic membrane roughness, with significant increase in Runx2 mRNA levels. These results show that bone marrow stem cells demonstrate similar cytoskeletal adaptations to low-magnitude high-frequency mechanical loads both during quiescence and osteogenesis, potentially becoming more sensitive to additional loads by increased structural stiffness.Article Citation - WoS: 25Citation - Scopus: 27Osteogenic Differentiation of Mesenchymal Stem Cells on Random and Aligned Pan/Ppy Nanofibrous Scaffolds(SAGE Publications, 2019) Selamet, Yusuf; İnce Yardımcı, Atike; Baskan, Öznur; Yılmaz, Selahattin; Meşe, Gülistan; Özçivici, EnginThe aim of this study was to develop random and aligned polyacrilonitrile (PAN)/polypyrrole (PPy) nanofibrous scaffolds by electrospinning technique for osteogenic differentiation of mesenchymal stem cells. Nanofibers were fabricated successfully as straight, smooth, and free from bead formation. The average diameter of random and aligned nanofibers was 268(+/- 49) nm and 225(+/- 72) nm, respectively. Alignment process increased the tensile strength of nanofibers 3.9-fold, while the tensile strain of nanofibers decreased by 78%. PAN/PPy nanofibers were hydrophilic with the contact angle value of about 32 degrees and alignment did not affect the contact angle value. Random and aligned PAN/PPy nanofibers were investigated as a scaffold material for osteogenic differentiation of D1 ORL UVA mouse bone marrow mesenchymal stem cells. Cells were able to attach and grow on nanofibers confirmed by cell viability results. Stem cells that were cultured with osteogenic induction were able to mineralize on electrospun nanofibers based on alizarin red and Von Kossa dye staining. For aligned PPy nanofibers, mineralization occurred in the fiber alignment direction. Consequently, PAN/PPy nanofibrous mats in both random and aligned forms would be potential candidates for bone tissue engineering.Article Citation - WoS: 8Citation - Scopus: 11Application of Low Intensity Mechanical Vibrations for Bone Tissue Maintenance and Regeneration(TÜBİTAK, 2016) Ölçüm, Melis; Baskan, Öznur; Karadaş, Özge; Özçivici, EnginPhysical exercise is beneficial for bone tissue health, yet its usage is limited for preventing osteoporosis. Even though natural for the bone tissue from development to homeostasis, mechanical loads present with a multitude of physical parameters, including amplitude, duration, frequency, and distribution. Utilizing the most beneficial parameters of mechanical loads may potentiate a nonpharmaceutical tool for biotechnology to prevent and treat bone loss related to aging, bedrest, sedentary lifestyles, weightlessness, and other diseases. Low intensity vibrations (LIVs) consist of mechanical loads with amplitudes smaller than loads prescribed by habitual activity, with a higher frequency. In this review, literature covering LIV signal application on bone tissue and cellular and molecular level is presented. Studies indicate that LIV signals are safe, anabolic, and anticatabolic for skeletal tissue and are of great significance in regenerative medicine applications.Article Citation - WoS: 5Citation - Scopus: 5Effects of Intraperitoneal Injection of Allogeneic Bone Marrow-Derived Mesenchymal Stem Cells on Bronchiolitis Obliterans in Mice Model(Tehran University of Medical Sciences, 2017) Işık, Sakine; Uzuner, Nevin; Karaman, Meral; Karaman, Özkan; Kıray, Müge; Kozanoğlu, İlknur; Bağrıyanık, Hüsnü Alper; Arıkan Ayyıldız, Zeynep; Kartal Yandım, Melis; Baran, YusufBone marrow-derived mesenchymal stem cells (BMSCs) can ameliorate a variety of lung diseases such as asthma, lung fibrosis, and acute lung injury by its anti-inflammatory and immunmodulatory effects. In this study, we developed a mouse model of bronchiolitis obliterans (BO) and evaluated the effects of the intraperitoneal administration of BMSCs on lung histopathology and cytokine levels. 25 BALB/c mice were divided into four groups; control group (Group I), BO developed and 1x106 BMSCs-injected group (Group II), non-BO, 1x106 BMSCs-injected group (Group III), and BO developed and saline-injected group (Group IV). Histological and immunohistochemical findings of the lung tissue and the migration of BMSCs to the lung were evaluated using light and confocal microscopy techniques. Confocal microscopy evaluations showed that there was no noteworthy amount of BMSCs in the lung tissue of group III while significant amount of BMSCs was detected in group II. Wall thicknesses of terminal bronchiole and periterminal bronchiolar collagen deposition were significantly lower in group II compared to the group IV (p<0.05). Furthermore, according to the immunohistochemical staining results, CD3, CD4, CD8, CD20, CD68 and neutrophil elastase positive immune cells of group II were stained more positive than group IV cells (p<0.05). IFN-ã IL-2 and TNF-á levels in bronchoalveolar lavage fluid (BALF) were significantly lower in group II compared to group IV (p<0.05). The findings of this study indicate that intraperitoneally administered BMSCs have potent effects on histopatological changes of the lung tissue and cytokine levels in the murine model of BO.Article Citation - WoS: 12Citation - Scopus: 15Effects of Cell-Mediated Osteoprotegerin Gene Transfer and Mesenchymal Stem Cell Applications on Orthodontically Induced Root Resorption of Rat Teeth(Oxford University Press, 2017) Amuk, Nisa Gül; Kurt, Gökmen; Baran, Yusuf; Seyrantepe, Volkan; Kartal Yandım, Melis; Adan, Aysun; Akyıldız Demir, Seçil; Kiraz, Yağmur; Sönmez, Mehmet FatihAim: The aim of this study is to evaluate and compare therapeutic effects of mesenchymal stem cell (MSCs) and osteoprotegerin (OPG) gene transfer applications on inhibition and/or repair of orthodontically induced inflammatory root resorption (OIIRR). Materials and methods: Thirty Wistar rats were divided into four groups as untreated group (negative control), treated with orthodontic appliance group (positive control), MSCs injection group, and OPG transfected MSCs [gene therapy (GT) group]. About 100 g of orthodontic force was applied to upper first molar teeth of rats for 14 days. MSCs and transfected MSC injections were performed at 1st, 6th, and 11th days to the MSC and GT group rats. At the end of experiment, upper first molar teeth were prepared for genetical, scanning electron microscopy (SEM), fluorescent microscopy, and haematoxylin eosin-tartrate resistant acid phosphatase staining histological analyses. Number of total cells, number of osteoclastic cells, number of resorption lacunae, resorption area ratio, SEM resorption ratio, OPG, RANKL, Cox-2 gene expression levels at the periodontal ligament (PDL) were calculated. Paired t-test, Kruskal-Wallis, and chi-square tests were performed. Results: Transferred MSCs showed marked fluorescence in PDL. The results revealed that number of osteoclastic cells, resorption lacunae, resorption area ratio, RANKL, and Cox-2 were reduced after single MSC injections significantly (P < 0.05). GT group showed the lowest number of osteoclastic cells (P < 0.01), number of resorption lacunae, resorption area ratio, and highest OPG expression (P < 0.001). Conclusions: Taken together all these results, MSCs and GT showed marked inhibition and/or repair effects on OIIRR during orthodontic treatment on rats.Article Citation - WoS: 40Citation - Scopus: 47Gelatin-Based 3d Conduits for Transdifferentiation of Mesenchymal Stem Cells Into Schwann Cell-Like Phenotypes(Elsevier Ltd., 2017) Uz, Metin; Büyüköz, Melda; Sharma, Anup D.; Sakaguchi, Donald S.; Alsoy Altınkaya, Sacide; Mallapragada, Surya K.In this study, gelatin-based 3D conduits with three different microstructures (nanofibrous, macroporous and ladder-like) were fabricated for the first time via combined molding and thermally induced phase separation (TIPS) technique for peripheral nerve regeneration. The effects of conduit microstructure and mechanical properties on the transdifferentiation of bone marrow-derived mesenchymal stem cells (MSCs) into Schwann cell (SC) like phenotypes were examined to help facilitate neuroregeneration and understand material-cell interfaces. Results indicated that 3D macroporous and ladder-like structures enhanced MSC attachment, proliferation and spreading, creating interconnected cellular networks with large numbers of viable cells compared to nanofibrous and 2D-tissue culture plate counterparts. 3D-ladder-like conduit structure with complex modulus of ∼0.4 × 106 Pa and pore size of ∼150 μm provided the most favorable microenvironment for MSC transdifferentiation leading to ∼85% immunolabeling of all SC markers. On the other hand, the macroporous conduits with complex modulus of ∼4 × 106 Pa and pore size of ∼100 μm showed slightly lower (∼65% for p75, ∼75% for S100 and ∼85% for S100β markers) immunolabeling. Transdifferentiated MSCs within 3D-ladder-like conduits secreted significant amounts (∼2.5 pg/mL NGF and ∼0.7 pg/mL GDNF per cell) of neurotrophic factors, while MSCs in macroporous conduits released slightly lower (∼1.5 pg/mL NGF and 0.7 pg/mL GDNF per cell) levels. PC12 cells displayed enhanced neurite outgrowth in media conditioned by conduits with transdifferentiated MSCs. Overall, conduits with macroporous and ladder-like 3D structures are promising platforms in transdifferentiation of MSCs for neuroregeneration and should be further tested in vivo. Statement of Significance This manuscript focuses on the effect of microstructure and mechanical properties of gelatin-based 3D conduits on the transdifferentiation of mesenchymal stem cells to Schwann cell-like phenotypes. This work builds on our recently accepted manuscript in Acta Biomaterialia focused on multifunctional 2D films, and focuses on 3D microstructured conduits designed to overcome limitations of current strategies to facilitate peripheral nerve regeneration. The comparison between conduits fabricated with nanofibrous, macroporous and ladder-like microstructures showed that the ladder-like conduits showed the most favorable environment for MSC transdifferentiation to Schwann-cell like phenotypes, as seen by both immunolabeling as well as secretion of neurotrophic factors. This work demonstrates the importance of controlling the 3D microstructure to facilitate tissue engineering strategies involving stem cells that can serve as promising approaches for peripheral nerve regeneration.Article Citation - WoS: 26Citation - Scopus: 32Low-Intensity Vibrations Normalize Adipogenesis-Induced Morphological and Molecular Changes of Adult Mesenchymal Stem Cells(SAGE Publications Inc., 2017) Baskan, Öznur; Meşe, Gülistan; Özçivici, EnginBone marrow mesenchymal stem cells that are committed to adipogenesis were exposed daily to high-frequency low-intensity mechanical vibrations to understand molecular, morphological and ultrastructural adaptations to mechanical signals during adipogenesis. D1-ORL-UVA mouse bone marrow mesenchymal stem cells were cultured with either growth or adipogenic medium for 1 week. Low-intensity vibration signals (15 min/day, 90 Hz, 0.1 g) were applied to one group of adipogenic cells, while the other adipogenic group served as a sham control. Cellular viability, lipid accumulation, ultrastructure and morphology were determined with MTT, Oil-Red-O staining, phalloidin staining and atomic force microscopy. Semiquantitative reverse transcription polymerase chain reaction showed expression profile of the genes responsible for adipogenesis and ultrastructure of cells. Low-intensity vibration signals increased viability of the cells in adipogenic culture that was reduced significantly compared to quiescent controls. Low-intensity vibration signals also normalized the effects of adipogenic condition on cell morphology, including area, perimeter, circularization and actin cytoskeleton. Furthermore, low-intensity vibration signals reduced the expression of some adipogenic markers significantly. Mesenchymal stem cells are sensitive and responsive to mechanical loads, but debilitating conditions such as aging or obesity may steer mesenchymal stem cells toward adipogenesis. Here, daily application of low-intensity vibration signals partially neutralized the effects of adipogenic induction on mesenchymal stem cells, suggesting that these signals may provide an alternative and/or complementary option to reduce fat deposition.