Researcher:
Sokullu, Emel

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Faculty Member

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Emel

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Sokullu

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Sokullu, Emel
Sokullu, Emel Şadiye

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2020 - 202320

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Researcher Of Publications: search.filters.isAuthorOfPublication.6d5f59da-7080-47b5-aeb4-48dcbb30ccc3

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    Insights into the critical role of exosomes in the brain; from neuronal activity to therapeutic efects
    (Springer, 2022) Saghati, Sepideh; Karimipour, Mohammad; Rahbarghazi, Reza; N/A; Heidarzadeh, Morteza; Sokullu, Emel; PhD Student; Faculty Member; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); Graduate School of Health Sciences; School of Medicine; N/A; 163024
    Exo are natural nano-sized vesicles with an endosomal origin that maintain cell-to-cell communications in a paracrine manner. Owing to their physicochemical properties, Exo transfer various types of bioactive metabolites from origin cells to the recipient cells, resulting in induction/inhibition of specific signaling pathways. Like different tissues, Exo are indispensable for the function of neural cells inside the brain parenchyma. Various aspects such as neurogenesis, microglial polarization, and angiogenesis are closely associated with the reciprocal interchanges of Exo between cells in a tightly regulated manner. Similar to physiological conditions, these particles can affect the progression of inflammatory responses following the onset of pathologies. The existence of several uptake exosomal mechanisms, such as receptor-mediated endocytosis, and high penetration capacity into the deep layers of the brain makes Exo promising bio-shuttles for the alleviation of pathological conditions. Like astrocytes, stem cells can release Exo into the surrounding niche with neuroprotective properties regenerative potential. Whether and how Exo can initiate the essential signals required for neurogenesis has not been fully understood. In this review, we will try to elaborate on the putative therapeutic role of Exo in the dynamic activity of neuronal cells.
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    Cytoprotective and cytofunctional effect of polyanionic polysaccharide alginate and gelatin microspheres on rat cardiac cells
    (Elsevier, 2020) Amini, Hassan; Hashemzadeh, Shahriar; Saberianpour, Shirin; Rahbarghazi, Reza; Nouri, Mohammad; N/A; Heidarzadeh, Morteza; Mamipour, Mina; Yousefi, Mohammadreza; Sokullu, Emel; PhD Student; PhD Student; PhD Student; Faculty Member; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); Graduate School of Health Sciences; Graduate School of Health Sciences; Graduate School of Health Sciences; School of Medicine; N/A; N/A; N/A; 163024
    This study investigated the cyto-functional effect of Alginate-Gelatin microspheres on rat cardiomyoblasts after 7 days. Rat cardiomyoblasts were encapsulated inside Alginate-Gelatin microspheres via application of high voltage rate and dropping in a stirring CaCl2 solution. The swelling rate, biodegradation, and mechanical features were measured. Cell viability was assessed using MTT. Cell membrane integrity was monitored via calculation supernatant SCOT, SGPT, CPK, and LDH. We also measured SOD, GPx, and anti-oxidant capacity. Protein levels of Nrl-2 and PCCG-1 alpha were detected via western blotting. The cyto-functional activity of encapsulated cells was monitored using real-time PCR assay targeting the expression of Connexin-43, alpha-actinin, and myosin light chain. Data showed suitable biodegradation and swelling rate in Alginate-gelatin microspheres by time. 7-day incubation of rat cells inside microspheres did not exert cytotoxicity compared to control cells (p> 0.05). The release of SGPT, SGOT, CPK, and LDH in encapsulated cells was significantly decreased compared to the control group (p < 0.05). We also found enhanced anti-oxidant capacity and SOD and GPx activity in cells after being-encapsulated inside Alginate-Gelatin microspheres (p < 0.05) coincided with increased Nrf-2 synthesis (p < 0.05) compared to control cells. The expression of Connexin-43, alpha-actinin, and myosin light chain was significantly up-regulated, showing cyto-functional effect of Alginate-Gelatin microspheres after 7-days
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    Three-dimensional neurovascular co-culture inside a microfluidic invasion chemotaxis chip
    (Mary Ann Liebert, Inc, 2022) Cücük, Levent; Polat, İrem; N/A; Department of Mechanical Engineering; Sokullu, Emel; Taşoğlu, Savaş; Faculty Member; Faculty Member; Department of Mechanical Engineering; School of Medicine; College of Engineering; 163024; 291971
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    Exosomes-based therapy of stroke, an emerging approach toward recovery
    (Bmc, 2022) Seyedaghamiri, Fatemehsadat; Salimi, Leila; Ghaznavi, Dara; Rahbarghazi, Reza; Sokullu, Emel; Faculty Member; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); School of Medicine; 163024
    Based on clinical observations, stroke is touted as one of the specific pathological conditions, affecting an individual's life worldwide. So far, no effective treatment has been introduced to deal with stroke post-complications. Production and release of several neurotrophic factors by different cells exert positive effects on ischemic areas following stroke. As a correlate, basic and clinical studies have focused on the development and discovery of de novo modalities to introduce these factors timely and in appropriate doses into the affected areas. Exosomes (Exo) are non-sized vesicles released from many cells during pathological and physiological conditions and participate in intercellular communication. These particles transfer several arrays of signaling molecules, like several neurotrophic factors into the acceptor cells and induce specific signaling cascades in the favor of cell bioactivity. This review aimed to highlight the emerging role of exosomes as a therapeutic approach in the regeneration of ischemic areas.
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    Investigation of neurovascular effects of marine-derived molecules in 3D micro frame co-culture model
    (Mary Ann Liebert, Inc., 2022) Polat, İrem; Özkaya, Ferhat Can; Lahloubd, Mohamed-Farid; Ebrahimd, Weaam; Sokullu, Emel; Faculty Member; N/A; School of Medicine; N/A; 163024; 57111
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    Activation of toll-like receptor signaling in endothelial progenitor cells dictates angiogenic potential: from hypothesis to actual state
    (Springer, 2021) Avci, Cigir Biray; Saberianpour, Shirin; Ahmadi, Mahdi; Hassanpour, Mehdi; Bagheri, Hesam Saghaei; Rezaie, Jafar; Talebi, Mehdi; Roodbari, Fatemeh; Darabi, Masoud; Rahbarghazi, Reza; N/A; Heidarzadeh, Morteza; Sokullu, Emel; PhD Student; Faculty Member; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); Graduate School of Health Sciences; School of Medicine; N/A; 163024
    Human endothelial progenitor cells (EPCs) were isolated from cord blood samples and enriched by magnetic activated cell sorting method based on the CD133 marker. Cells were incubated with different doses of bacterial lipopolysaccharide, ranging from 2, 5, 10, 50, 100, 200, 250, 500, to 1000 mu g/ml, for 48 h. The cell survival rate was determined by using MTT assay. To confirm activation of the toll-like receptor signaling pathway, PCR array analysis was performed. Protein levels of ERK1/2, p-ERK1/2, NF-kappa B and TRIF proteins were measured using western blotting. The content of TNF-alpha and lipoprotein lipase activity were analyzed by immunofluorescence imaging. Flow cytometric analysis of CD31 was performed to assess the maturation rate. Cell migration was studied by the Transwell migration assay. The expression of genes related to exosome biogenesis was measured using real-time PCR analysis. In vivo gel plug angiogenesis assay was done in nude mice. Lipopolysaccharide changed endothelial progenitor cells' survival in a dose-dependent manner with maximum viable cells in groups treated with 2 mu g/ml. PCR array analysis showed the activation of toll-like signaling pathways after exposure to LPS (p<0.05). Western blotting analysis indicated an induction of p-ERK1/2 and Erk1/2, NF-kappa B and TRIF in LPS-treated EPCs compared with the control (p<0.05). Immunofluorescence staining showed an elevation of TNF-alpha and lipoprotein lipase activity after lipopolysaccharide treatment (p<0.05). Lipopolysaccharide increased EPC migration and expression of exosome biogenesis-related genes (p<0.05). In vivo gel plug analysis revealed enhanced angiogenesis in cells exposed to bacterial lipopolysaccharide. Data highlighted the close relationship between the toll-like receptor signaling pathway and functional activity in EPCs.
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    3D bioprinted glioma models
    (Iop Publishing Ltd, 2022) N/A; N/A; N/A; N/A; N/A; N/A; N/A; Department of Mechanical Engineering; Yığcı, Defne; Sarabi, Misagh Rezapour; Üstün, Merve; Atçeken, Nazente; Sokullu, Emel; Önder, Tuğba Bağcı; Taşoğlu, Savaş; Undergraduate Student; PhD Student; PhD Student; Researcher; Faculty Member; Faculty Member; Faculty Member; Department of Mechanical Engineering; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); School of Medicine; Graduate School of Sciences and Engineering; Graduate School of Sciences and Engineering; N/A; School of Medicine; School of Medicine; College of Engineering; N/A; N/A; N/A; N/A; 163024; 184359; 291971
    Glioma is one of the most malignant types of cancer and most gliomas remain incurable. One of the hallmarks of glioma is its invasiveness. Furthermore, glioma cells tend to readily detach from the primary tumor and travel through the brain tissue, making complete tumor resection impossible in many cases. To expand the knowledge regarding the invasive behavior of glioma, evaluate drug resistance, and recapitulate the tumor microenvironment, various modeling strategies were proposed in the last decade, including three-dimensional (3D) biomimetic scaffold-free cultures, organ-on-chip microfluidics chips, and 3D bioprinting platforms, which allow for the investigation on patient-specific treatments. The emerging method of 3D bioprinting technology has introduced a time- and cost-efficient approach to create in vitro models that possess the structural and functional characteristics of human organs and tissues by spatially positioning cells and bioink. Here, we review emerging 3D bioprinted models developed for recapitulating the brain environment and glioma tumors, with the purpose of probing glioma cell invasion and gliomagenesis and discuss the potential use of 4D printing and machine learning applications in glioma modelling.
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    Protein corona and exosomes: new challenges and prospects
    (BioMed Central Ltd, 2023) Zarebkohan, Amir; Rahbarghazi, Reza; Heidarzadeh, Morteza; Sokullu, Emel; PhD Student; Faculty Member; Graduate School of Health Sciences; School of Medicine; N/A; 163024
    Recent advances in extracellular vesicle (EVs) detection and isolation methods have led to the development of novel therapeutic modalities. Among different types of EVs, exosomes (Exos) can transfer different signaling biomolecules and exhibit several superior features compared to whole-cell-based therapies. Therapeutic factors are normally loaded into the Exo lumen or attached to their surface for improving the on-target delivery rate and regenerative outcomes. Despite these advantages, there are several limitations in the application of Exos in in vivo conditions. It was suggested that a set of proteins and other biological compounds are adsorbed around Exos in aqueous phases and constitute an external layer named protein corona (PC). Studies have shown that PC can affect the physicochemical properties of synthetic and natural nanoparticles (NPs) after introduction in biofluids. Likewise, PC is generated around EVs, especially Exos in in vivo conditions. This review article is a preliminary attempt to address the interfering effects of PC on Exo bioactivity and therapeutic effects. Video Abstract.
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    Preclinical experimental applications of miRNA loaded BMSC extracellular vesicles
    (2021) Çetin, Zafer; Saygılı, Eyüp, I; Gorgisen, Gökhan; Sokullu, Emel; Faculty Member; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); School of Medicine; 163024
    Bone marrow mesenchymal stem cells have been investigated for many years, especially for tissue regeneration, and have inherent limitations. One of the rapidly developing fields in the scientific world in recent years is extracellular vesicles. Especially, bone marrow mesenchymal stem cell originated extracellular vesicles are known to have positive contributions in tissue regeneration, and these extracellular vesicles have also been used as gene transfer systems for cellular therapy. Through gene expression analysis and bioinformatics tools, it is possible to determine which genes have changed in the targeted tissue or cell and which miRNAs that can correct this gene expression disorder. This approach connecting the stem cell, extracellular vesicles, epigenetics regulation and bioinformatics fields is one of the promising areas for the treatment of diseases in the future. With this review, it is aimed to present the studies carried out for the use of bone marrow stem cell-derived extracellular vesicles loaded with targeted miRNAs in different in vivo and in vitro human disease models and to discuss recent developments in this field.
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    Application of exosomes for the alleviation of COVID-19-related pathologies
    (Wiley, 2022) Rezabakhsh, Aysa; Mahdipour, Mahdi; Nourazarian, Alireza; Habibollahi, Paria; Avcı, Çığır Biray; Rahbarghazi, Reza; Sokullu, Emel; Faculty Member; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); School of Medicine; 163024
    The pandemic of COVID-19 caused worldwide concern. Due to the lack of appropriate medications and the inefficiency of commercially available vaccines, lots of efforts are being made to develop de novo therapeutic modalities. Besides this, the possibility of several genetic mutations in the viral genome has led to the generation of resistant strains such as Omicron against neutralizing antibodies and vaccines, leading to worsening public health status. Exosomes (Exo), nanosized vesicles, possess several therapeutic properties that participate in intercellular communication. The discovery and application of Exo in regenerative medicine have paved the way for the alleviation of several pathologies. These nanosized particles act as natural bioshuttles and transfer several biomolecules and anti-inflammatory cytokines. To date, several approaches are available for the administration of Exo into the targeted site inside the body, although the establishment of standard administration routes remains unclear. As severe acute respiratory syndrome coronavirus 2 primarily affects the respiratory system, we here tried to highlight the transplantation of Exo in the alleviation of COVID-19 pathologies.