Tıp Fakültesi / Faculty of Medicine

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

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Author: search.filters.author.Karaoz, Erdal

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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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    The Promising Effects of Bmp2 Transfected Mesenchymal Stem Cells on Human Osteosarcoma
    (2021) Sari, Ahmet Sinan; Demircay, Emre; Ozturk, Ahmet; Terzi, Aysen; Karaoz, Erdal; 0000-0002-5429-1929; 0000-0003-1274-4288; 34377054; AAL-2368-2021
    Selective targeting of transfected mesenchymal stem cells (MSCs) carrying specific antioncogenes to the tumor was suggested as a treatment option. Bone morphogenetic protein-2 (BMP2) was shown to inhibit the proliferation and aggressiveness of osteosarcoma (OS) cells. Here, we aimed to assess the homing efficiency of intraperitoneally administered hMSCs transfected with BMP2 to the tumoral site and their effects on OS using an orthotopic xenograft murine model. Orthotopic xenograft murine model of OS in six-week-old female NOD/SCID mice using 143B cells was established. hMSCs transfected with BMP2 (BMP2(+)hMSC) were used. In vivo experiments performed on four groups of mice that received no treatment, or intraperitoneally administered BMP2, hMSCs, and BMP2(+)hMSCs. Histopathological and immunohistochemical studies were used to evaluate the pathological identification and to assess the dimensions and necrotic foci of the tumor, the features of lung metastases, and immunostaining against p27, Ki-67, and caspase-3 antibodies. The osteogenic differentiation markers BMP2, BMP4, COL1A1, OPN, OCN and PF4 evaluated using RT-PCR. The tumor dimensions in the hMSCs group were significantly higher than those of the remaining groups (p < 0.01). The number of metastatic foci in the BMP2(+)hMSCs group was significantly lower than those of the other groups (p < 0.01). The current results showed that the intraperitoneal route could be efficiently used for targeting hMSCs to the tumoral tissues for effective BMP2 delivery. In this study, the effects of BMP2 transfected hMSCs on human OS and metastasis were promising for achieving osteogenic differentiation and reduced metastatic process.