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AKKOÇ, TUNÇ

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    PublicationOpen Access
    Mesenchymal stem cells differentiate to retinal ganglion-like cells in rat glaucoma model induced by polystyrene microspheres
    (2023-10-01) ERASLAN, MUHSİN; ÇERMAN, EREN; BOZKURT, SÜHEYLA; AKKOÇ, TUNÇ; ERASLAN M., ÇERMAN E., BOZKURT S., Genç D., Virlan A. T., Demir C. S., Akkoç T., Karaöz E., AKKOÇ T.
    Aim: The study aimed to evaluate the differentiation ability of intravitreally injected rat bone marrow-derived mesenchymal stem cells (rBM-MSCs) to retinal ganglion-like cells in a polystyrene microsphere induced rat glaucoma model. Materials and Methods: The glaucoma rat model was generated via intracameral injection of 7 microliter polystyrene microspheres. Green fluorescence protein-labeled (GFP) rBM-MSCs were transplanted intravitreally at or after induction of ocular hypertension (OHT), depending on the groups. By the end of the fourth week, flat-mount retinal dissection was performed, and labeled against Brn3a, CD90, GFAP, CD11b, Vimentin, and localization of GFP positive rBM-MSCs was used for evaluation through immunofluorescence staining and to count differentiated retinal cells by flow cytometry. From 34 male Wistar albino rats, 56 eyes were investigated. Results: Flow cytometry revealed significantly increased CD90 and Brn3a positive cells in glaucoma induced and with rBM-MSC injected groups compared to control(P = 0.006 and P = 0.003 respectively), sham-operated (P = 0.007 and P < 0.001 respectively), and only rBM-MSCs injected groups (P = 0.002 and P = 0.009 respectively). Immunofluorescence microscopy revealed differentiation of GFP labeled stem cells to various retinal cells, including ganglion-like cells. rBM-MSCs were observable in ganglion cells, inner and outer nuclear retinal layers in rBM-MSCs injected eyes. Conclusion: Intravitreally transplanted rBM-MSCs differentiated into retinal cells, including ganglion-like cells, which successfully created a glaucoma model damaged with polystyrene microspheres. Promisingly, MSCs may have a role in neuro-protection and neuro-regeneration treatment of glaucoma in the future.
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    SARS COV-2 PCR+ hastalarının peptivatör ile etkileşimi sonucu hafıza hücrelerinin incelenmesi
    (2023-05-25) AKSU, MEHMET BURAK; AKKOÇ, TUNÇ; Yurt C., Durmuş E. R., Sarıgül N., Eşme Y., Kılıç S., Tunca Z., Aksu M. B., Akkoç T.
    Giriş ve Amaç: SARS COV-2 virüsü, CD4+ ve CD8+ T hücrelerini ve B hücrelerini etkileyerek bağışıklığı aktive etmektedir. CD45RA T hücreleri, antijenleri hatırlamaması ile \"naive\" özelliklere sahipken CD45RO T hücreleri, antijenleri hatırlayıp çoğaldıkları için \"bellek\" T hücreleri olarak kabul edilir. Peptivator SARS-CoV-2 Select, SARS-CoV-2 spesifik CD4+ ve CD8+ T hücrelerini in vitro uyararak efektör sitokinlerin salgılanmasına sebep olup SARS-CoV-2 spesifik T hücrelerinin saptanmasına ve izolasyonuna olanak tanır. Bu çalışmadaki amacımız SARS-COV-2 hastalarının kanından elde edilen lenfositlerin peptivatör ile etkileşimi sonucu hafıza hücrelerinin incelenmesidir. Gereç ve Yöntem: Araştırmamız deneysel tiptedir. Marmara Üniversitesi Pendik Eğitim ve Araştırma Hastanesi Göğüs Hastalıkları polikliniğinde yatan Koronavirüs hastaları, araştırmanın evrenini oluşturmaktadır. T.C. Sağlık Bakanlığı Marmara Üniversitesi Pendik Eğitim ve Araştırma Hastanesi Göğüs Hastalıkları polikliniğinde Koronavirüs hastalığı sebebi ile yatan aşılı ve aşısız, PCR pozitif 18- 50 yaş arası 9 hastadan gönüllü olmaları kaydıyla kan örnekleri toplanmıştır. Hastalardan alınan periferik kanların bir kısmı ile tam kan immünfenotipleme analizi yapılmıştır. Hastalardan alınan periferik kanın bir kısmı ile de mononükleer hücre (PKMH) izolasyonu yapılıp uyarımsız (US), CDmix uyarımlı ve peptivatör ile uyarımı sonrasında akım sitometrisi kullanılarak analizi yapılmıştır. Bulgular: Flow sitometri tam kan immünfenotipleme analizlerinde CD45RO+ oranı aşısız olan grupta 93,6 (±6,76), aşılı grupta 94,2 (±6,07) olarak bulunmuştur. Hastalardan elde edilen PKMH’ler; US, CDmix ve Peptivatör ile kültür edildikten sonra flow sitometri analizlerinde US kültürde CD45RO+FoxP3 oranı aşısız grupta 8,29 (±4,62), aşılı grupta 3,5 (±2,19) olarak bulunmuştur. CDmix kültüründe CD45RO+FoxP3 oranı aşısız grupta 32,6 (±32,4), aşılı grupta 18,8 (±18,6) bulunmuştur. Peptivatör kültüründe CD45RO+Foxp3 oranı aşısız grupta 36,2 (±35,5), aşılı grupta ise 7,24 (±5,94) olarak bulunmuştur. Sonuç: COVID-19’da mRNA teknolojisi ile üretilen BioNTech/Pfizer aşısı enfeksiyon geçiren hastalarda hafıza hücre sayılarını aşısızlara göre arttırmaktadır. Peptivatör etkileşimi ise aşılı PCR+ grupta ve aşısız PCR+ grupta immün sistemi etkilediği ve hafıza hücrelerini arttırdığı gözlenmektedir.
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    Effects of different detergent-containing children's toothpastes on the viability, osteogenic and chondrogenic differentiation of human dental periodontal ligament stem cells and gingival stem cells in vitro
    (CHURCHILL LIVINGSTONE, 2021) AKKOÇ, TUNÇ; Birant, Sinem; Duran, Yazgul; Gokalp, Muazzez; Akkoc, Tunc; Seymen, Figen
    Background: Detergents are the most commonly used compounds in toothpastes due to their foaming and cleaning peoperties. This study aimed to investigate the effects of children's toothpastes with different detergent content on the viability, the osteogenic and chondrogenic differentiation potentials of human mesenchymal stem cells. Methods: The necessary tissues for human periodontal ligament mesenchymal stem cells (hPDLMSCs) and human gingival mesenchymal stem cells (hGMSCs) isolation were obtained during extraction of 10 impacted third molar teeth. The viability of the cells stimulated with different concentratiaons of Colgate, Sensodyne, Splat, Nenedent, Perlodent toothpaste solutions and complete Dulbocco's modified eagle medium (control group) were evaluated by using the flow cytometer. In addition, the osteogenic and chondrogenic differentiation potential of human gingival and periodontal ligament mesenchymal stem cells exposed to toothpaste solutions were examined morphologically. Datas were analyzed with IBM SPSS V23. One way ANOVA test was used to determine the differences between the groups for multiple comparisons, while the Tukey post-hoc test was used for pair wise comparisons in determining which groups differed. Results: A higher percentage of cell viability was detected in Control group at 20 %, 50 % and 80 % (p= 0.000) on hGMSCs. After the Control group, the highest cell viability ratios were observed in the detergent-free Splat group (p = 0.000) followed by the Sensodyne experimental group containing CABP (p= 0.000). While the cell viability rates in Nenedent group was found significantly higher than the Perlodent group at other concentrations except for 20 % concentration (p = 0.000). Colgate group had the lowest percentage of cell viability among the experimental groups at all concentrations on hPDMSCs (p = 0.000). The highest live cell ratios was detected in Control group (p = 0.000), followed by Splat and Sensodyne groups (p = 0.000). The cell viability ratios at 50 % concentration were higher in Perlodent group than Nenedent group (p = 0.000). The highest osteogenic and chondrogenic differentiation potential of mesenchymal stem cells stimulated with different toothpaste was determined in Control and Splat group. Conclusions: As a result of the findings, it was observed that toothpaste containing SLS had a more negative effect on the viability of the cells and the differentiation potentials than the other groups.
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    Asthma immunotherapy and treatment approaches with mesenchymal stem cells
    (FUTURE MEDICINE LTD, 2020) AKKOÇ, TUNÇ; Akkoc, Tunc; Genc, Deniz
    Asthma is a chronic inflammatory disease of the airways where exaggerated T helper 2 immune responses and inflammatory mediators play a role. Current asthma treatment options can effectively suppress symptoms and control the inflammatory process; however, cannot modulate the dysregulated immune response. Allergen-specific immunotherapy is one of the effective treatments capable of disease modification. Injecting allergens under the skin in allergen-specific immunotherapy can reduce asthma and improve the sensitivity of the lungs, however, has a risk of severe reactions. Mesenchymal stem cells have immunoregulatory activity with their soluble mediators and contact dependent manner. In this review, we focus on the current treatment strategies with mesenchymal stem cells in asthma as a new therapeutic tool and compare those with immunotherapy.
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    PublicationOpen Access
    FIP teşhisi konmuş kedilerden elde edilen periferal kan mononükleer hücreler ile kedi overinden elde edilen mezenkimal kök hücrenin immünolojik araştırılması
    (2023-05-25) AKSU, MEHMET BURAK; AKKOÇ, TUNÇ; Güven N., Erhan M. N., Karayusuf K., Doğanay K., Kılıç S., Tunca Z., Aksu M. B., Akkoç T.
    Giriş ve Amaç: Coronavirüsler hem insanlarda hem de hayvanlarda hafiften son derece şiddetli enfeksiyonlara kadar değişkenlik göstermektedir. Coronaviruslar çoğunlukla gastroentestinal ve solunum sistemi enfeksiyonlarına neden olurken bazıları ensefaliti ve hepatite neden olmaktadır. Kedilerin Enfeksiyöz Peritonitisi (FIP) ise kedi coronavirüslerinin (FCoV) neden olduğu bir enfeksiyondur. Çalışmamızda ise kedi ovaryum kaynaklı mezenkimal kök hücrelerin (O-MKH), FIP teşhisi konmuş kedilerden elde edilen periferal kan mononükleer hücrelere (PKMH) etkisinin in vitro ortamda araştırılıp değerlendirilmesi amaçlanmaktadır. Gereç ve Yöntem: Projemizde veteriner kliniğinde FIP tanısı konulmuş 5-13 yaşlarındaki kediler çalışmaya dahil edilecektir. Bu süreçte veteriner kliniğine gelen hastalardan FIP pozitif çıkan kedilerden hasta sahiplerinden alınan onam sonrasında 5cc periferal kan örneği alınacak ve Marmara Üniversitesi Tıp Fakültesi immünoloji anabilim dalında PKMH izole edilecektir. Ayrıca, kedi ovaryumlardan MKH izolasyonu gerçekleştirilecektir. İzole edilen PKMH ile O-MKH\"ların (+/-) ko-kültür işlemleri gerçekleştirilecektir. 5 günlük kültür işleminden sonra O-MKH\"nin FIP hasta PMKH\"larının canlılıkları üzerindeki etkileri akım sitometri yöntemi ile analiz edilecektir. Gerekli etik ve kurum izinleri alınmıştır. Bulgular: Yapılan ko-kültür çalışması sonrasında akım sitometri yöntemi ile PKMH’lerin canlılıklarındaki değişimler kıyaslanmıştır. Yapılan analizler sonucunda FIP kedilerin PKMH’ları MKH’nın olmadığı durumlarda canlılık oranı 55.6 (±5.2) iken MKH varlığında canlılıklarının 70.13 (±2.1)’e yükseldiği görülmüştür. Buna ek olarak, apoptoz geçiren PKMH’ların oranı MKH yokluğunda 34.7 (±4.4) iken MKH varlığında 12.7’e (±1.8) düştüğü gözlenmiştir. Hastalardaki PKMH’ların sağlıklı kedilerin durumları ile kıyaslandığında ise FIP hastası PKMH’ların canlılıkları MKH varlığında sağlıklı kedilerin PKMH’ların canlılık seviyesine yükseldiği görülmüştür. Sonuç: FIP hastalığına sahip olan kedilerin PKMH’larındaki canlılık oranının sağlıklı kediye kıyasla canlılık oranının beklendiği gibi daha düşük olduğu görülmüştür. Yine de MKH’nın varlığında FIP hastası kedilerin PKMH’larındaki canlılık seviyesinin sağlıklı kedilerin PKMH’lerin canlılık oranına yükseldiği görülmüştür. Ayrıca, MKH’ların apoptoz geçiren PKMH’ları FIP hastası kedilerde düşürdüğü gözlenmiştir. Elde edilen bu veriler çerçevesinde MKH’ların FIP hastalarında olumlu etkisi olduğu gözlenmektedir.
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    PublicationOpen Access
    Cytotoxicity of NeoMTA Plus, ProRoot MTA and Biodentine on human dental pulp stem cells
    (ELSEVIER TAIWAN, 2021-07) AKKOÇ, TUNÇ; Birant, Sinem; Gokalp, Muazzez; Duran, Yazgul; Koruyucu, Mine; Akkoc, Tunc; Seymen, Figen
    Background/purpose: Dental pulp stem cells (DPSCs) play a crucial role in the tis-sue healing process through odontoblast like cell differentiation. The aim of this study was to evaluate the biocompatibility and compare the potential invitro cytotoxic effects of NeoMTA Plus, ProRootMTA and Biodentine on human dental pulp stem cells (hDPSCs). Materials and methods: To assess the effects of NeoMTA Plus, ProRoot MTA and Biodentine ex-tracts at 1st, 3rd and 7th d on hDPCs, cell populations was determined by flow cytometry using an Annexin V detection kit. The data were analyzed statistically using the Kruskal-Wallis test. A p < 0.05 was considered as statistically significant. Results: All groups showed cell viability similar to that of the control group on 1st, 3rd and 7th d. Although Biodentine exhibited higher cell viability rates than the other material groups, no statistically significant differences were noted between the sampled days (p > 0.05). Conclusion: All materials extracts are not cytotoxic and do not induce apoptosis in the hDPSCs. These results suggest that all the tested materials can lead to positive outcomes when used as reparative biomaterials. (c) 2020 Association for Dental Sciences of the Republic of China. Publishing services by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons. org/licenses/by-nc-nd/4.0/).
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    Mesenchymal stem cells derived from human dental follicle modulate the aberrant immune response in atopic dermatitis
    (FUTURE MEDICINE LTD, 2021) BARIŞ, SAFA; Zibandeh, Noushin; Genc, Deniz; Ozgen, Zuleyha; Duran, Yazgul; Goker, Kamil; Baris, Safa; Ergun, Tulin; Akkoc, Tunc
    Background: Atopic dermatitis (AD) is an inflammatory cutaneous disorder. The advancements in the understanding of AD immunological pathogenesis have caused the development of therapies that suppress the dysregulated immune response. We aimed to evaluate the immunomodulatory effect of dental stem cells (dental follicle-mesenchymal stem cells [DF-MSCs]) on AD patients. Materials & methods: We investigated the immunoregulatory potential of DF-MSCs on T cell response in AD and compared them with psoriasis and healthy individuals and the underlying mechanisms. Results: DF-MSCs significantly reduced Fas, FasL and TNFR II frequency in T cells, increased naive T cell population while reducing memory T cell, decreased inflammatory cytokine levels and promoted Tregs frequency in the AD population. Conclusion: These results imply that DF-MSCs are modulating inflammation through decreasing T cell apoptosis, inducing Treg expansion and stabilizing cytokine levels. Lay abstract Background: Atopic dermatitis (AD) is an inflammatory cutaneous disorder characterized by immune-mediated inflammation and epidermal barrier dysfunction. There is no definite solution for the treatment of AD. We aimed to evaluate the immunomodulatory and immunosuppressive effect of dental stem cells (dental follicle-mesenchymal stem cell [DF-MSCs]) on AD. Materials & methods: We investigated the immunoregulatory potential of DF-MSCs on inflammatory response in AD and compared them with psoriasis and healthy individuals and the mechanism underlying it. Results: DF-MSCs significantly reduced apoptosis-related markers in immune cells, decreased inflammatory cytokine levels and promoted Treg frequency in the AD. Conclusion: Our findings provide basic evidence for the potential role of DF-MSCs as a cellular therapy option in the treatment of AD and shed light on future clinical studies.
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    PublicationOpen Access
    Canine adipose tissue stem cells induced with toll-like receptor agonists exhibit antibacterial activity against multi drug resistant pathogens
    (2023-03-01) AKSU, MEHMET BURAK; AKKOÇ, TUNÇ; AKSU M. B., Yanilmaz O., AKKOÇ T.
    Infections caused by antibiotic-resistant pathogens pose a major threat worldwide. There is an urgent need to develop effective strategies to solve this problem. The antibacterial activity of adult mesenchymal stem cells (MSCs) has recently been determined against various bacterial isolates. New approaches, such as Toll-like receptor activation, were used to enhance their antibacterial potency. This study examines the antibacterial activity of TLR agonist (TLR2/TLR1 and/or TLR2/TLR6) activated adipose-derived canine MSCs (AD-MSCs) on multidrug resistant isolates including Staphylococcus aureus, Escherichia coli, Enterococcus faecalis, and Pseudomonas aeruginosa regarding bacterial growth, and minimum inhibitory concentration (MIC) determination. Effects on bacterial morphology were assessed by electron microscopy. Our results showed that the AD-MSCs conditioned medium primed with different TLR agonists inhibited the growth of E. coli and S. aureus, but it had a decreased effect on E. faecalis and P. aeruginosa. Despite this, AD-MSCs conditioned medium prepared with the combination of TLR agonists exhibited antibacterial activity against all isolates. These findings were in parallel with MIC levels of conditioned media. We conclude that adipose-derived canine MSCs primed with TLR agonists (TLR2/TLR1 and TLR2/TLR6 combination) possess antimicrobial activity against multi-drug resistant isolates of E. coli, S. aureus, E. faecalis and P. aeruginosa. Further studies for testing in in vivo models are being planned to assess the potential application of AD-MSCs as an adjunct treatment modality for multi drug resistant infections.
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    Immunomodulatory and Tissue-preserving Effects of Human Dental Follicle Stem Cells in a Rat Cecal Ligation and Perforation Sepsis Model
    (ELSEVIER SCIENCE INC, 2020) GÜL, FETHİ; Sarica, Leyla Topcu; Zibandeh, Noushin; Genc, Deniz; Gul, Fethi; Akkoc, Tolga; Kombak, Erdem Faruk; Cinel, Leyla; Akkoc, Tunc; Cinel, Ismail
    Background. Mesenchymal stem cells may be used for the treatment of sepsis. Dental follicle stem cells (DFSCs) are easily accessible but have not been studied in vivo or in clinical trials in sepsis models. Aim of the study. We aim to elucidate DFSC effects on host immunological functions in a rat cecal ligation and perforation (CLP) sepsis model. Methods. Adult male rats were categorized into group 1 (sham procedure SP), group 2 (SP + 1 x 10(6) DFSCs administered 0 h after SP), group 3 (CLP + saline), group 4 (CLP 1 x 10(6) DFSCs administered 0 h after CLP), and group 5 (CLP + 1 x 10(6) DFSCs administered 4 h after CLP). Green fluorescent protein-labeled cells were used for imaging. Histopathological examination of ileal tissues was performed. Results. A significant increase in the percentage of CD4+/CD25+/Foxp3+ Treg cells in groups 4 and 5 occurred compared with that in group 3. No significant changes in CD3+/CD4+ helper T-cells and CD3+/CD8+ cytotoxic T-cells were observed. Treatment with DFSCs at 4 h significantly decreased the level of TNF-alpha compared with that in group 3. No significant changes in IL-10 levels and lymphocyte proliferation suppression were observed. During histopathological examination, no high scoring (Chiu scores: 3 or 4) rats were observed in the curative treatment group (group 5). Conclusions. Treatment with DFSC after 4 h of sepsis induction downregulates tissue inflammatory responses by decreasing TNF-alpha levels and increasing Treg cell ratio. This also has a protective effect on intestinal tissues during sepsis. (C) 2020 IMSS. Published by Elsevier Inc.
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    Mesenchymal stem cells in asthma
    (Springer, 2020) AKKOÇ, TUNÇ; Akkoc T.
    Asthma is one of the worldwide respiratory health problem that affect children and adult. Current treatment strategies such as conventional and allergen immunotherapy still fall behind. Mesenchymal stem cells (MSCs) have wide regenerative capacity and immunoregulatory activity with their wide range of secretions and contact dependent manner. In this review, we focus on the current treatment strategies for asthma and MSCs as a new therapeutic tool. © Springer Nature Switzerland AG 2019.