Browsing by Author "Ovali, Ercument"

Now showing 1 - 10 of 10

Decellularization of Trachea With Combined Techniques for Tissue-Engineered Trachea Transplantation
(KOREAN SOC OTORHINOLARYNGOL, 2019-01-01) Batioglu-Karaaltin, Aysegul; Ovali, Ercument; Karaaltin V, Mehmet; Yener, Murat; Yilmaz, Mehmet; Epupoglu, Fatma; Yilmaz, Yetkin Zeki; Bozkurt, Erol Rustu; Demir, Necdet; Konuk, Esma; Bozdag, Ergun Sureyya; Yigit, Ozgur; Cansiz, Harun
Objectives. The purpose of this study is to shorten the decellularization time of trachea by using combination of physical, chemical, and enzymatic techniques. Methods. Approximately 3.5-cm-long tracheal segments from 42 New Zealand rabbits (3.5 +/- 0.5 kg) were separated into seven groups according to decellularization protocols. After decellularization, cellular regions, matrix and strength and endurance of the scaffold were followed up. Results. DNA content in all groups was measured under 50 ng/mg and there was no significant difference for the glycosaminoglycan content between group 3 (lyophilization+deoxycholic acid+de-oxyribonuclease method) and control group (P=0.46). None of the decellularized groups was different than the normal trachea in tensile stress values (P>0.05). Glucose consumption and lactic acid levels measured from supernatants of all decellularized groups were close to group with cells only (76 mg/dl, and 53 mg/L). Conclusion. Using combination methods may reduce exposure to chemicals, prevent the excessive influence of the matrix, and shorten the decellularization time.
Factors Affecting the Population of Mesenchymal Stem Cells in Adipose-Derived Stromal Vascular Fraction
(GALENOS PUBL HOUSE, 2022-01-01) Sari, E. Cigdem Karadag; Ovali, Ercument
Background: Recently, the adipose tissue-derived stromal vascular fraction has become the most popular source for obtaining mesenchymal stem cells because it is less expensive and is easier to perform than bone marrow concentrate harvesting. However, no study has investigated the factors affecting the mesenchymal stem cell population in adipose tissue derived stromal vascular fraction. Understanding the interaction of patient factors with the mesenchymal stem cell count and cell viability in adipose tissue-derived stromal vascular fraction could provide crucial information for surgeons to improve patient selection and outcomes.Aims: To evaluate the factors affecting the mesenchymal stem cell count, total cell count, and cell viability in adipose tissue-derived stromal vascular fraction.Study Design: Retrospective cross-sectional study.Methods: This study retrospectively reviewed the medical records of 30 patients who underwent liposuction to harvest adipose tissue - derived stromal vascular fraction at our stem cell center. Operative variables, such as lipoaspirate amount and donor areas from the stromal vascular fraction harvesting site, included the entire abdomen and lower abdomen. We recorded the mesenchymal stem cell population, cell viability, and cell count of stromal vascular fraction, and we analyzed the results to determine statistical significance.Results: The factors that were found to be significantly related are as follows
Gamma-irradiated SARS-CoV-2 vaccine candidate, OZG-38.61.3, confers protection from SARS-CoV-2 challenge in human ACEII-transgenic mice
(NATURE PORTFOLIO, 2021-01-01) Turan, Raife Dilek; Tastan, Cihan; Kancagi, Derya Dilek; Yurtsever, Bulut; Karakus, Gozde Sir; Ozer, Samed; Abanuz, Selen; Cakirsoy, Didem; Tumentemur, Gamze; Demir, Sevda; Seyis, Utku; Kuzay, Recai; Elek, Muhammer; Kocaoglu, Miyase Ezgi; Ertop, Gurcan; Arbak, Serap; Elmas, Merve Acikel; Hemsinlioglu, Cansu; Ng, Ozden Hatirnaz; Akyoney, Sezer; Sahin, Ilayda; Kayhan, Cavit Kerem; Tokat, Fatma; Akpinar, Gurler; Kasap, Murat; Kocagoz, Ayse Sesin; Ozbek, Ugur; Telci, Dilek; Sahin, Fikrettin; Yalcin, Koray; Ratip, Siret; Ince, Umit; Ovali, Ercument
The SARS-CoV-2 virus caused the most severe pandemic around the world, and vaccine development for urgent use became a crucial issue. Inactivated virus formulated vaccines such as Hepatitis A and smallpox proved to be reliable approaches for immunization for prolonged periods. In this study, a gamma-irradiated inactivated virus vaccine does not require an extra purification process, unlike the chemically inactivated vaccines. Hence, the novelty of our vaccine candidate (OZG-38.61.3) is that it is a non-adjuvant added, gamma-irradiated, and intradermally applied inactive viral vaccine. Efficiency and safety dose (either 10(13) or 10(14) viral RNA copy per dose) of OZG-38.61.3 was initially determined in BALB/c mice. This was followed by testing the immunogenicity and protective efficacy of the vaccine. Human ACE2-encoding transgenic mice were immunized and then infected with the SARS-CoV-2 virus for the challenge test. This study shows that vaccinated mice have lowered SARS-CoV-2 viral RNA copy numbers both in oropharyngeal specimens and in the histological analysis of the lung tissues along with humoral and cellular immune responses, including the neutralizing antibodies similar to those shown in BALB/c mice without substantial toxicity. Subsequently, plans are being made for the commencement of Phase 1 clinical trial of the OZG-38.61.3 vaccine for the COVID-19 pandemic.
Generation of Bone Tissue Using Adipose Tissue-derived Stem Cells
(BEZMIALEM VAKIF UNIV, 2021-01-01) Baygol, Emre Gonenc; Guneren, Ethem; Karaaltin, Mehmet Veli; Canter, Halil Ibrahim; Ozturk, Kahraman; Ovali, Ercument; Ozpur, Mustafa Aykut; Yildiz, Kemalettin; Eyuboglu, Fatma
Objective: Bone grafts and even bone substitutes do not meet all of the requirements of bony reconstructions. The aim of this study was to generate bone tissue from autologous adipose tissue-derived mesenchymal stem cells (ATDMSCs) and decellularised bone allografts. Methods: A 1.5 cm bone defect developed in the middle third of the rabbit's ulna. Reconstructions were carried out using miniplate and screws and interpositional autogenous bone grafts according to the designs of the groups: (1) No touch, (2) cryopreserved, (3) decellularised and (4) ATDMSCs-implanted decellularised bones. Before implantation, ATDMSCs in the last group were labelled with Q-dot and identified microscopically. Results: Graft recovery and irregular callus formation were observed in the first, second and forth groups. In the first group, the organisation of Haversian systems, the structure of the lacunae and the presence of canaliculi ossiums were observed
Mesenchymal Stem Cell Treatment for Steroid Refractory Graft-versus-Host Disease in Children: A Pilot and First Study from Turkey
(HINDAWI LTD, 2016-01-01) Erbey, Fatih; Atay, Didem; Akcay, Arzu; Ovali, Ercument; Ozturk, Gulyuz
This study evaluated the efficacy of mesenchymal stem cells (MSCs) from bone marrow of a third-party donor for refractory aGVHD. We report the first experience using MSCs to treat refractory aGVHD in 33 pediatric patients undergoing allogeneic HSCT from Turkey. Totally, 68 doses of bone marrow derived MSCs were infused. The median dose of MSC was 1.18 x 10(6) cells per kg body weight. Overall, complete response (CR) was documented in 18 patients, partial response (PR) was documented in 7 patients, and no response (NR) was documented in 8 patients. The 2-year estimated probability of overall survival (OS) for patients achieving CR and PR/NR was 63.8\% and 29.4\%, respectively (p = 0.0002). While the cumulative incidence of transplant related mortality (TRM) at day 100 after first MSC infusion was 46.6\% in PR/NR patients, there was no any TRM at day 100 after first MSC infusion in CR patients (p = 0.001). Twelve patients developed chronic GVHD (cGVHD)
Mutational landscape of SARS-CoV-2 genome in Turkey and impact of mutations on spike protein structure
(PUBLIC LIBRARY SCIENCE, 2021-01-01) Hatirnaz Ng, Ozden; Akyoney, Sezer; Sahin, Ilayda; Soykam, Huseyin Okan; Bayram Akcapinar, Gunseli; Ozdemir, Ozkan; Kancagi, Derya Dilek; Sir Karakus, Gozde; Yurtsever, Bulut; Kocagoz, Ayse Sesin; Ovali, Ercument; Ozbek, Ugur
The Coronavirus Disease 2019 (COVID-19) was declared a pandemic in March 2020 by the World Health Organization (WHO). As of May 25th, 2021 there were 2.059.941 SARS-COV2 genome sequences that have been submitted to the GISAID database, with numerous variations. Here, we aim to analyze the SARS-CoV-2 genome data submitted to the GISAID database from Turkey and to determine the variant and clade distributions by the end of May 2021, in accordance with their appearance timeline. We compared these findings to USA, Europe, and Asia data as well. We have also evaluated the effects of spike protein variations, detected in a group of genome sequences of 13 patients who applied to our clinic, by using 3D modeling algorithms. For this purpose, we analyzed 4607 SARS-CoV-2 genome sequences submitted by different lab centers from Turkey to the GISAID database between March 2020 and May 2021. Described mutations were also introduced in silico to the spike protein structure to analyze their isolated impacts on the protein structure. The most abundant clade was GR followed by G, GH, and GRY and we did not detect any V clade. The most common variant was B.1, followed by B.1.1, and the UK variant, B.1.1.7. Our results clearly show a concordance between the variant distributions, the number of cases, and the timelines of different variant accumulations in Turkey. The 3D simulations indicate an increase in the surface hydrophilicity of the reference spike protein and the detected mutations. There was less surface hydrophilicity increase in the Asp614Gly mutation, which exhibits a more compact conformation around the ACE-2 receptor binding domain region, rendering the structure in a ``down{''} conformation. Our genomic findings can help to model vaccination programs and protein modeling may lead to different approaches for COVID-19 treatment strategies.
Preclinical Assessment of Efficacy and Safety Analysis of CAR-T Cells (ISIKOK-19) Targeting CD19-Expressing B-Cells for the First Turkish Academic Clinical Trial with Relapsed/Refractory ALL and NHL Patients
(GALENOS YAYINCILIK, 2020-01-01) Tastan, Cihan; Kancagi, Derya Dilek; Turan, Raife Dilek; Yurtsever, Bulut; Cakirsoy, Didem; Abanuz, Selen; Yilanci, Muhammet; Seyis, Utku; Ozer, Samed; Mert, Selin; Kayhan, Cavit Kerem; Tokat, Fatma; Elmas, Merve Acikel; Birdogan, Selcuk; Arbak, Serap; Yalcin, Koray; Sezgin, Aslihan; Kizilkilic, Ebru; Hemsinlioglu, Cansu; Ince, Umit; Ratip, Siret; Ovali, Ercument
Objective: Relapsed and refractory CD19-positive B-cell acute lymphoblastic leukemia (ALL) and non-Hodgkin lymphoma (NHL) are the focus of studies on hematological cancers. Treatment of these malignancies has undergone recent transformation with the development of new gene therapy and molecular biology techniques, which are safer and well-tolerated therapeutic approaches. The CD19 antigen is the most studied therapeutic target in these hematological cancers. This study reports the results of clinical-grade production, quality control, and in vivo efficacy processes of ISIKOK-19 cells as the first academic clinical trial of CAR-T cells targeting CD19-expressing B cells in relapsed/refractory ALL and NHL patients in Turkey. Materials and Methods: We used a lentiviral vector encoding the CD19 antigen-specific antibody head (FMC63) conjugated with the CD8-CD28-CD3 zeta
Preclinical efficacy and safety analysis of gamma-irradiated inactivated SARS-CoV-2 vaccine candidates
(NATURE RESEARCH, 2021-01-01) Karakus, Gozde Sir; Tastan, Cihan; Kancagi, Derya Dilek; Yurtsever, Bulut; Tumentemur, Gamze; Demir, Sevda; Turan, Raife Dilek; Abanuz, Selen; Cakirsoy, Didem; Seyis, Utku; Ozer, Samed; Elibol, Omer; Elek, Muhammer; Ertop, Gurcan; Arbale, Serap; Elmas, Merve Acikel; Hermsinlioglu, Canso; Kocagoz, Ayse Sesin; Ng, Ozden Hatirnaz; Akyoney, Sezer; Sahin, Ilayda; Ozbek, Ugur; Telci, Dilek; Sahin, Fikrettin; Yalcin, Koray; Ratip, Siret; Ovali, Ercument
COVID-19 outbreak caused by SARS-CoV-2 created an unprecedented health crisis since there is no vaccine for this novel virus. Therefore, SARS-CoV-2 vaccines have become crucial for reducing morbidity and mortality. In this study, in vitro and in vivo safety and efficacy analyzes of lyophilized vaccine candidates inactivated by gamma-irradiation were performed. The candidate vaccines in this study were OZG-3861 version 1(V1), an inactivated SARS-CoV-2 virus vaccine, and SK-01 version 1 (V1), a GM-CSF adjuvant added vaccine. The candidate vaccines were applied intradermally to BALB/c mice to assess toxicity and immunogenicity. Preliminary results in vaccinated mice are reported in this study. Especially, the vaccine models containing GM-CSF caused significant antibody production with neutralization capacity in absence of the antibody-dependent enhancement feature, when considered in terms of T and B cell responses. Another important finding was that the presence of adjuvant was more important in T cell in comparison with B cell response. Vaccinated mice showed T cell response upon restimulation with whole inactivated SARS-CoV-2 or peptide pool. This study shows that the vaccines are effective and leads us to start the challenge test to investigate the gamma-irradiated inactivated vaccine candidates for infective SARS-CoV-2 virus in humanized ACE2+ mice.
Risk of Neoplastic Squall Downstream Cytokine Storm of COVID-19 in Male Patients
(GALENOS YAYINCILIK, 2020-01-01) Turkeri, Levent; Ovali, Ercument
SARS-CoV-2 isolation and propagation from Turkish COVID-19 patients
(2004-01-01) Tastan, Cihan; Yurtsever, Bulut; Karakus, Gozde Sir; Kancagi, Derya Dilek; Demir, Sevda; Abanuz, Selen; Seyis, Utku; Yildirim, Mulazim; Kuzay, Recai; Elibol, Omer; Arbak, Serap; Elmas, Merve Acikel; Birdogan, Selcuk; Sezerman, Osman Ugur; Kocagoz, Aye Sesin; Yalcin, Koray; Ovali, Ercument
The novel coronavirus pneumonia, which was named later as coronavirus disease 2019 (COVID-19), is caused by the severe acute respiratory syndrome coronavirus 2, namely SARS-CoV-2. It is a positive-strand RNA virus that is the seventh coronavirus known to infect humans. The COVID-19 outbreak presents enormous challenges for global health behind the pandemic outbreak. The first diagnosed patient in Turkey has been reported by the Republic of Turkey Ministry of Health on March 11, 2020. In May, over 150,000 cases in Turkey, and 5.5 million cases around the world have been declared. Due to the urgent need for a vaccine and antiviral drug, isolation of the virus is crucial. Here, we report 1 of the first isolation and characterization studies of SARS-CoV-2 from nasopharyngeal and oropharyngeal specimens of diagnosed patients in Turkey. This study provides an isolation and replication methodology,and cell culture tropism of the virus that will be available to the research communities.