Tıp Fakültesi / Faculty of Medicine

Permanent URI for this collectionhttps://hdl.handle.net/11727/1403

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Subject: search.filters.subject.Mesenchymal stem cells

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    Effects of Mesenchymal Stem Cells and VEGF on Liver Regeneration Following Major Resection
    (2016) Adas, Gokhan; Koc, Bora; Adas, Mine; Duruksu, Gokhan; Subasi, Cansu; Kemik, Ozgur; Kemik, Ahu; Sakiz, Damlanur; Kalayci, Mustafa; Purisa, Sevim; Unal, Seda; Karaoz, Erdal; 27094936
    The study aims to determine the effects of mesenchymal stem cell (MSC) therapy and a combination therapy of MSCs transfected with vascular endothelial growth factor (VEGF) for liver regeneration after major resection. Thirty-eight rats were divided into four groups: group 1: control (sham operation); group 2: control (70 % hepatic resection); group 3: 70 % hepatic resection + systemically transplanted MSCs; and group 4: 70 % hepatic resection + systemically transplanted MSCs transfected with the VEGF gene. MSCs were injected via the portal vein route in study groups 3 and 4. Expression levels of VEGF, fibroblast growth factor (FGF), platelet-derived growth factor (PDGF), epidermal growth factor (EGF), transforming growth factor (TGF), hepatocyte growth factor (HGF), and augmenter of liver regeneration (ALR) were analyzed in the remnant liver tissue. We investigated the levels of angiogenic factors, VEGF-receptor, angiopoietin-1 (Angpt1) and Angpt2. Biochemical parameters of liver function in blood samples were measured and a histologic assessment of the livers was performed. The postoperative liver weight and volume of each rat were measured 14 days after surgery. The expression levels of all measured growth factors were significantly increased in groups 3 and 4 compared to the control groups. The levels of Angpt1 and Angpt2 correlated with levels of VEGF and thus were also significantly higher in the study groups. There were significant differences between the estimated liver weights and volumes of group 4 and the resected controls in group 2. With the exception of portal inflammation, levels of all histological parameters were observed to be higher in MSC-treated groups when compared with the resected controls in group 2. Transplanted stem cells and MSCs transfected with VEGF significantly accelerated many parameters of the healing process following major hepatic resection. After the injection of MSCs and VEGF-transfected MSCs into the portal vein following liver resection, they were engrafted in the liver. They increased bile duct and liver hepatocyte proliferation, and secreted many growth factors including HGF, TGF beta, VEGF, PDGF, EGF, and FGF via paracrine effects. These effects support liver function, regeneration, and liver volume/weight.
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    Effects of Intraperitoneal Injection of Allogeneic Bone Marrow-derived Mesenchymal Stem Cells on Bronchiolitis Obliterans in Mice Model
    (2017) Isik, Sakine; Uzuner, Nevin; Karaman, Meral; Karaman, Ozkan; Kiray, Muge; Kozanoglu, Ilknur; Bagriyanik, Husnu Alper; Arikan-Ayyildiz, Zeynep; Yandim, Melis Kartal; Baran, Yusuf; https://orcid.org/0000-0002-5268-1210; 28732434; AAE-1241-2021
    Bone 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 1x10(6) BMSCs-injected group (Group II), non-BO, 1x10(6) 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-gamma IL-2 and TNF-alpha 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.
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    Intraperitoneal Mesenchymal Stem Cell Administration Ameliorates Allergic Rhinitis in The Murine Model
    (2017) Isik, Sakine; Karaman, Meral; Adan, Aysun; Kiray, Muge; Bagriyanik, Husnu Alper; Sozmen, Sule Caglayan; Kozanoglu, Ilknur; Karaman, Ozkan; Baran, Yusuf; Uzuner, Nevin; https://orcid.org/0000-0002-5268-1210; 27380271; AAE-1241-2021
    Previous studies showed that bone marrow-derived mesenchymal stem cells (BMSCs) could ameliorate a variety of immune-mediated and inflammatory diseases due to their immunomodulatory and anti-inflammatory effects. In this study, we developed a mouse model of ovalbumin (OVA) induced allergic inflammation in the upper airways and evaluated the effects of the intraperitoneal administration of BMSCs on allergic inflammation. Twenty-five BALB/c mice were divided into five groups; group I (control group), group II (sensitized and challenged with OVA and treated with saline-placebo group), group III (sensitized and challenged with OVA and treated with 1 x 10(6) BMSCs), group IV (sensitized and challenged with OVA and treated with 2 x 10(6) BMSCs), and group V (sensitized and challenged with phosphate buffered saline (PBS) and treated with 1 x 10(6) BMSCs). Histopathological features (number of goblet cells, eosinophils and mast cells, basement membrane, epithelium thickness, and subepithelial smooth muscle thickness) of the upper and lower airways and BMSCs migration to nasal and lung tissue were evaluated using light and confocal microscopes. Levels of cytokines in the nasal lavage fluid and lung tissue supernatants were measured using enzyme-linked immunosorbent assay (ELISA). Confocal microscopic analysis showed that there was no significant amount of BMSCs in the nasal and lung tissues of group V. However, significant amount of BMSCs were observed in group III and IV. In OVA-induced AR groups (group II, III, and IV), histopathological findings of chronic asthma, such as elevated subepithelial smooth muscle thickness, epithelium thickness, and number of goblet and mast cells, were determined. Furthermore, the number of nasal goblet and eosinophil cells, histopathological findings of chronic asthma, and IL-4, IL-5, IL-13, and NO levels was significantly lower in both BMSCs-treated groups compared to the placebo group. Our findings indicated that histopathological findings of chronic asthma were also observed in mice upon AR induction. BMSCs migrated to the nasal and lung tissues following intraperitoneal delivery and ameliorated to the airway remodeling and airway inflammation both in the upper and lower airways via the inhibition of T helper (Th) 2 immune response in the murine model of AR.
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    Adrenergic receptor behaviors of mesenchymal stem cells obtained from different tissue sources and the effect of the receptor blockade on differentiation
    (2021) Maytalman, Erkan; Alizadeh Yegani, Arash; Kozanoglu, Ilknur; Aksu, Fazilet; 0000-0002-5268-1210; 34323168; AAE-1241-2021
    In this study, it was aimed to analyze behavioral changes of adrenergic receptors (ARs) in first three passages and osteogenic/adipogenic differentiation of mesenchymal stem cells (MSCs) derived from placenta fetal membrane (FM) and bone marrow (BM). It was also aimed to evaluate effects of receptor blockade on differentiation. We obtained first three passages of MSCs from placenta and BM samples. For cell identification, the cells were analyzed by flow cytometry using CD34, CD45 and CD3, CD105 antibodies in each passage. The effects of propranolol and phenoxybenzamine at incremental doses were analyzed by MTT. In addition, cell cultures were separately maintained with the blockers or without after second passage. After each passage and differentiation, alpha 1A, alpha 1B, alpha 2A, alpha 2B, beta 1, beta 2, beta 3 AR-mRNA expressions analyzed by RT-qPCR technique. BMP6 and PPARG mRNA expressions only after differentiation and passage 3 were analyzed. A microscopic examination was also performed. Our results showed that AR expression behaviors were different in MSCs obtained from different tissue sources. In particular, alpha(1A)-AR and alpha(2A)-AR were expressed with considerably high coefficients in differentiation under blocker effect in BM-derived MSCs. No such coefficients were observed in any group of placental MSCs. In addition, it was found that the blockers stimulated adipogenesis in BM-derived MSCs during osteogenic differentiation. MSCs exhibit protein expressions that vary according to source of tissue and differentiation. Given that MSCs from different sources are used for repair and modulation, our study makes implications of this variable expression intriguing in the clinical practice.
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    Biological behaviors of muscarinic receptors in mesenchymal stem cells derived from human placenta and bone marrow
    (2020) Yegani, Arash Alizadeh; Maytalman, Erkan; Kozanoglu, Ilknur; Terzi, Menderes Yusuf; Aksu, Fazilet; 0000-0002-5268-1210; 32405354; AAE-1241-2021
    Objective(s): Cells perform their functional activities by communicating with each other through endogenous substances and receptors. Post-translation, stem cells function properly in new host tissue by carrying specific cell surface receptors. We aimed to characterize muscarinic receptor subtypes in mesenchymal stem cells (MSCs) together with osteogenic and adipogenic differentiation markers. Materials and Methods: mRNA levels of 5 muscarinic receptor subtypes (CHRM1 to 5), BMP-6, and PPAR gamma during osteogenic and adipogenic differentiation, under the effect of atropine blockade, were measured in MSCs obtained from human fetal membrane (FM) and bone marrow (BM). Additionally, the effect of atropine on differentiation in the 1st, 2nd, and 3rd passages of MSCs, obtained from human FM and BM, were analyzed by RT-qPCR. Results: CHRM1 mRNA levels increased in the FM group, while decreasing in the BM group. We found significant decreases in CHRM3 and CHRM5 mRNA levels in FM and BM groups, respectively. Atropine had variable effects based on cell source and receptor type. BMP-6 mRNA levels in differentiated osteogenic cells increased significantly compared to undifferentiated cells in both FM and BM groups. In MSCs derived from both sources, PPAR gamma mRNA levels in differentiated adipogenic cells increased significantly. Atropine showed no effect on MSCs differentiation. Conclusion: These results indicate that expressions of muscarinic receptors in MSCs derived from BM and FM can vary and these cells keep the potential of osteogenic and adipogenic differentiation in vitro. Besides, atropine had no effect on adipogenic and osteogenic differentiation of MSCs.