Researcher:
Heidarzadeh, Morteza

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PhD Student

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Morteza

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Heidarzadeh

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Heidarzadeh, Morteza

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2020 - 20239

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Researcher Of Publications: search.filters.isAuthorOfPublication.23587241-ba14-44d9-b896-9132a58e0c6f

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Now showing 1 - 9 of 9
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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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    Electrospun polyurethane/poly (ɛ-caprolactone) nanofibers promoted the attachment and growth of human endothelial cells in static and dynamic culture conditions
    (Elsevier, 2021) Karkan, Sonia Fathi; Rahbarghazi, Reza; Davaran, Soodabeh; Kaleybar, Leila Shafiei; Khoshfetrat, Ali Baradar; Zolali, Elmira; Akbarzadeh, Abolfazl; N/A; Heidarzadeh, Morteza; PhD Student; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); Graduate School of Health Sciences; N/A
    In this study, the angiogenic capacity of human endothelial cells was studied after being plated on the surface of polyurethane-poly caprolactone (PU/PCL) scaffolds for 72 h. In this study, cells were designated into five different groups, including PU, PU/PCL (2:1), PU/PCL (1:1); PU/PCL (1:2); and PCL. Data revealed that the PU/PCL (2:1) composition had a higher modulus and breakpoint in comparison with the other groups (p < 0.05). Compared to the other groups, the PU/PCL scaffold with a molar ratio of 2:1 had lower the contact angle theta and higher tensile stress (p < 0.05). The mean size of the PU nanofibers was reduced after the addition of PCL (p 0.05). Based on our data, the culture of endothelial cells on the surface of PU/PCL (2:1) did not cause nitrosative stress and cytotoxic effects under static conditions compared to cells plated on a conventional plastic surface (p 0.05). Based on data from the static condition, we fabricated a tubular PU/PCL (2:1) construct for six-day dynamic cell culture inside loop air-lift bioreactors. Scanning electron microscopy showed the attachment of endothelial cells to the luminal surface of the PU/PCL scaffold. Cells were flattened and aligned under the culture medium flow. Immunofluorescence imaging showed the attachment of cells to the luminal surface indicated by blue nuclei on the luminal surface. These data demonstrated that the application of PU/PCL substrate could stimulate endothelial cells activity under static and dynamic conditions.
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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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    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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    PublicationOpen Access
    Distinct chemical composition and enzymatic treatment induced human endothelial cells survival in acellular ovine aortae
    (BioMed Central, 2021) Rahbarghazi, Reza; Saberianpour, Shirin; Delkhosh, Aref; Amini, Hassan; Hassanpour, Mehdi; 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
    Objective: the current experiment aimed to assess the impact of detergents such as 3% Triton X-100, 1% peracetic acid, 1% Tween-20, and 1% SDS in combination with Trypsin–EDTA on acellularization of ovine aortae after 7 days. Results: Hematoxylin–Eosin staining showed an appropriate acellularization rate in ovine aortae, indicated by a lack of cell nuclei in the tunica media layer. DAPI staining confirmed the lack of nuclei in the vascular wall after being exposed to the combination of chemical and enzymatic solutions. Verhoeff-Van Gieson staining showed that elastin fibers were diminished in acellular samples compared to the control group while collagen stands were unchanged. CCK-8 survival assay showed enhanced viability in human umbilical vein endothelial cells 5 days after being cultured on decellularized samples compared to the cells cultured on a plastic surface (p < 0.05). SEM imaging showed flattening of endothelial cells on the acellular surface.
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    PublicationOpen Access
    Exosomal delivery of therapeutic modulators through the blood-brain barrier; promise and pitfalls
    (BioMed Central, 2021) Eslami Abriz, Aysan; Zarebkohan, Amir; Rahbarghazi, Reza; Özdemir, Yasemin Gürsoy; Kaya, Mehmet; Sokullu, Emel; Heidarzadeh, Morteza; Faculty Member; Faculty Member; PhD Student; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); School of Medicine; Graduate School of Health Sciences; 170592; 10486; 163024; N/A
    Nowadays, a large population around the world, especially the elderly, suffers from neurological inflammatory and degenerative disorders/diseases. Current drug delivery strategies are facing different challenges because of the presence of the BBB, which limits the transport of various substances and cells to brain parenchyma. Additionally, the low rate of successful cell transplantation to the brain injury sites leads to efforts to find alternative therapies. Stem cell byproducts such as exosomes are touted as natural nano-drug carriers with 50-100 nm in diameter. These nano-sized particles could harbor and transfer a plethora of therapeutic agents and biological cargos to the brain. These nanoparticles would offer a solution to maintain paracrine cell-to-cell communications under healthy and inflammatory conditions. The main question is that the existence of the intact BBB could limit exosomal trafficking. Does BBB possess some molecular mechanisms that facilitate the exosomal delivery compared to the circulating cell? Although preliminary studies have shown that exosomes could cross the BBB, the exact molecular mechanism(s) beyond this phenomenon remains unclear. In this review, we tried to compile some facts about exosome delivery through the BBB and propose some mechanisms that regulate exosomal cross in pathological and physiological conditions.
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    PublicationOpen Access
    Does the global outbreak of COVID-19 or other viral diseases threaten the stem cell reservoir inside the body?
    (Springer, 2021) Bagheri, Hesam Saghaei; Karimipour, Mohammad; Rajabi, Hadi; Rahbarghazi, Reza; 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
    The COVID-19 pandemic has profoundly influenced public health and contributed to global economic divergences of unprecedented dimensions. Due to the high prevalence and mortality rates, it is then expected that the consequence and public health challenges will last for long periods. The rapid global spread of COVID-19 and lack of enough data regarding the virus pathogenicity multiplies the complexity and forced governments to react quickly against this pandemic. Stem cells represent a small fraction of cells located in different tissues. These cells play a critical role in the regeneration and restoration of injured sites. Because of their specific niche and a limited number of stem cells, the key question is whether there are different anti-viral mechanisms against viral infection notably COVID-19. Here, we aimed to highlight the intrinsic antiviral resistance in different stem cells against viral infection. These data could help us to understand the possible viral infections in different stem cells and the activation of specific molecular mechanisms upon viral entrance.
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    PublicationOpen Access
    An examination of the putative role of melatonin in exosome biogenesis
    (Frontiers, 2021) Amini, Hassan; Rezabakhsh, Aysa; Hassanpour, Mehdi; Hashemzadeh, Shahriar; Ghaderi, Shahrouz; Rahbarghazi, Reza; Reiter, Russel J.; Heidarzadeh, Morteza; Sokullu, Emel; PhD Student; Faculty Member; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); School of Medicine; Graduate School of Health Sciences; N/A; 163024
    During the last two decades, melatonin has been found to have pleiotropic effects via different mechanisms on its target cells. Data are abundant for some aspects of the signaling pathways within cells while other casual mechanisms have not been adequately addressed. From an evolutionary perspective, eukaryotic cells are equipped with a set of interrelated endomembrane systems consisting of intracellular organelles and secretory vesicles. Of these, exosomes are touted as cargo-laden secretory vesicles that originate from the endosomal multivesicular machinery which participate in a mutual cross-talk at different cellular interfaces. It has been documented that cells transfer various biomolecules and genetic elements through exosomes to sites remote from the original cell in a paracrine manner. Findings related to the molecular mechanisms between melatonin and exosomal biogenesis and cargo sorting are the subject of the current review. The clarification of the interplay between melatonin and exosome biogenesis and cargo sorting at the molecular level will help to define a cell's secretion capacity. This review precisely addresses the role and potential significance of melatonin in determining the efflux capacity of cells via the exosomal pathway. Certain cells, for example, stem cells actively increase exosome efflux in response to melatonin treatment which accelerates tissue regeneration after transplantation into the injured sites.