A Novel Virtue in Stem Cell Research: Exosomes and Their Role in Differentiation

Abdik, H. | Avsar Abdik, E. | Hızlı Deniz, A.A. | Taşlı, P.N. | Şahin, Fikrettin

Book Part | 2019 | Advances in Experimental Medicine and Biology1144 , pp.133 - 146

In the past decade a number of different stem cell types have entered the clinical applications increasingly as a therapeutic option, due to their tissue maintenance capacity at the site where they localize. Although it was initially thought that conferral of resilience to damaged tissue largely depends on the stem cells themselves through orchestration of signaling among the local epithelial and immune systems at the injury site, recent findings point out that the remarkable regenerative capacity of stem cells is rather due to their nanovesicular products that emerge as the new active players of tissue repair processes. Among these . . . extracellular vesicles exosomes generated particularly by stem cells have been receiving a substantial interest both in the fields of stem cell biology and extracellular vesicles. In this chapter fundamental facts about stem cell biology, biogenesis of extracellular vesicles and exosomes, their structure, and function are summarized. Moreover, properties of both tumor-derived exosomes as well as those derived from stem cells are discussed relatively in-depth in terms of their influence on proximal and distal tissue physiology. Last but not the least, among countless studies in an exploding field, we summarize those that attempt to unravel the complex signaling networks through which stem cell-derived exosomes alter the fate of differentiating stem cells as well as the molecular make-up of exosomes released from differentiating stem cells by conducting thorough proteomic and genomic analyses with the ultimate goal of identifying effector gene products mediating exosomal cues in stem cell biology. © 2019, Springer Nature Switzerland AG Daha fazlası Daha az

Cancer stem cells in metastasis therapy

Aydemir Çoban, E. | Şahin, Fikrettin

Book Part | 2018 | Advances in Experimental Medicine and Biology1089 , pp.97 - 113

Tumors consists of subpopulation of cells in which each subtype has contributes to tumor progression. Specifically one subtype known as cancer stem cells are associated with the initiation, progression, resistance to conventional therapies and metastasis. Metastasis is leading cause of cancer related deaths. Overall it is important to consider cancer as a whole in which a mutated cell proliferating indefinitely and forming its hierarchy consisting of subgroups with different molecular signatures. To be able to target this disease we need to evaluate every step including initiation, progression, survival, angiogenesis and finally mig . . .ration and repopulation. Cancer stem cells do play vital roles in each step however when metastasis can be stopped or eliminated we talk about saving a life or improving its quality. Considering how deeply these cancer stem like cells affect the tumor life and metastasis it is crucial to develop effective strategies against them. Metastatic cascade can also be directed by membrane derived vesicles specifically exosomes. Several studies show the role of exosomes in mediating cellular migration and pre-metastatic niche formation. During this chapter we wanted to explain in detail how the metastasis occur in tumor and how cancer stem cells contribute into the development of metastatic cascade and possibly suggest therapeutic approaches against cancer stem cells. © Springer Nature Switzerland AG 2018 Daha fazlası Daha az

Mesenchymal Stem Cells as Regulators of Carcinogenesis

Hayal, T.B. | Kıratlı, B. | Şişli, H.B. | Şahin, Fikrettin | Doğan, A.

Book Part | 2019 | Advances in Experimental Medicine and Biology1144 , pp.147 - 166

Mesenchymal Stem Cells (MSCs) are adult stem cells; isolated from various body parts including bone marrow, adipose tissue and dental tissue, have been characterized well and used in regenerative medicine applications. The promising potential of MSCs makes them great candidates in many disorders. It has been well known in the literature that MSCs interact with cancer cells and regulate the carcinogenesis process at different stages. The dual role of MSCs in cancer progression should be clearly identified at the physiological and molecular level to identify clinical potential in cancer treatment. The promoting or suppressive role of . . .MSCs in cancer is controlled by various growth factors, cytokines and chemokines which affect the cell proliferation, angiogenesis and metastasis. Although many studies have been conducted to explore MSC-cancer cell interactions, it is still unclear how MSCs communicate with cancer cells and tumor microenvironment. Further studies are required to investigate secreted factors and paracrine effects, tumor stroma environment, molecular regulators and downstream pathways that are involved in MSC-cancer interaction loop. MSC type, cancer type and stage specific phenotypic and transcriptomic profile changes should be identified in detail to improve clinical use of MSCs in cancer either as a target or as a tool. In the current book chapter, we review the literature to summarize current information about the MSC-cancer cell interactions in terms of soluble factors, angiogenesis, metastasis and drug resistance. The role of MSCs in tumor progression or suppression was discussed based on the current literature. © 2018, Springer Nature Switzerland AG Daha fazlası Daha az

A Genome-Wide Analysis of mRNA Expression in Human Tooth Germ Stem Cells Treated with Pluronic P85

Ataei, A. | Solovyeva, V.V. | Poorebrahim, M. | Blatt, N.L. | Salafutdinov, I.I. | Şahin, Fikrettin | Rizvanov, A.A.

Article | 2016 | BioNanoScience6 ( 4 ) , pp.392 - 402

Human tooth germ stem cells (hTGSCs) originate from the neural crest and have a great potential to be used in stem cell therapies. Our group has previously shown that Pluronics interact with stem cells and affect their biological function. Pluronics block copolymer (P85), a potential drug delivery agent in the micelle form, which was shown to improve stem cell expansion. However, it is not known how P85 treatment affects the transcription profile of hTGSCs. In the present study, we found substantial changes in the expression of 252 genes in response to P85 treatment by using Illumina microarray. The gene enrichment was carried out u . . .sing database for annotation, visualization, and integrated discovery (DAVID) and the results classified in several biologically meaningful clusters. Using bioinformatics tools, we constructed a global regulatory network of P85-modulated genes associated with stem cell differentiation pathways and multi-drug resistance (MDR) processes. In conclusion, our results were compatible with many of the P85-mediated biological processes and may help us to gain a better molecular understanding of P85 biological function. © 2016, Springer Science+Business Media New York Daha fazlası Daha az

Stem Cells Derived from Dental Tissues

Aydin, S. | Şahin, Fikrettin

Book Part | 2019 | Advances in Experimental Medicine and Biology1144 , pp.123 - 132

Stem cells are undifferentiated cells located in different parts of the body. The major role of stem cells is to restore of injured tissues. Since the discover of stem cells, they gained a big attention due to their differentiation and regeneration capacity. The main source of stem cells was known as bone marrow. However, different sources for obtaining stem cells were discovered. Dental tissues, a new source for stem cells, provide cells having mesenchymal stem cell characteristics such as fibroblast-like structure, expression of surface antigens specific for mesenchymal stem cells, regeneration ability, multilineage differentiatio . . .n capacity and immunomodulatory features. Dental pulp stem cells (DPSCs), dental follicle progenitor cells (DFPCs), stem cells from apical papilla (SCAP), tooth germ stem cells (TGSCs) and periodontal ligament stem cells (PDLSCs) are stem cells derived from dental tissues as well as stem cells from exfoliated deciduous teeth (SHED). Dental stem cells express mesenchymal stem cell markers like Stro-1, CD146, CD106, CD90, CD73 CD29 and CD13. However, they do not express hematopoietic stem cell markers such as CD11b, CD45 and CD34. Dental stem cells are able to undergo myogenic, chondrogenic, adipogenic, neurogenic, osteogenic and odontogenic differentiation. Thanks to these differentiation ability of dental stem cells, they can easily be manipulated in regenerative medicine. Dental stem cells, that can effortlessly be transfected, can also be used in cell therapy application. Immunomodulatory features of dental stem cells make them suitable candidates for the therapy of immune-related disorders. Dental stem cells with high potentials such as ability of self-renewal, mesenchymal stem cell characteristics, multilineage differentiation and immunomodulation are promising tool for in vitro and in vivo differentiation studies as well as the therapy of immune-related diseases. © 2019, Springer Nature Switzerland AG Daha fazlası Daha az

Immunomodulatory behavior of mesenchymal stem cells

Taşlı, P.N. | Bozkurt, B.T. | Kırbaş, O.K. | Deniz-Hızlı, A.A. | Şahin, Fikrettin

Book Part | 2018 | Advances in Experimental Medicine and Biology1119 , pp.73 - 84

The use of Mesenchymal Stem Cells (MSCs) in the treatment of diseases where immunomodulation impacts therapy is increasing steadily. Recent studies aim to achieve effective use of MSCs in treatment of Graft versus Host Disease (GvHD), Crohn’s disease and organ transplantations. The molecular mechanisms governing immunomodulatory properties of MSCs have not been fully understood, although current studies are indicating progress. Especially, in vitro studies and animal models provide a major contribution to our knowledge in clinical use of MSCs. The immunosuppressive and immune-enhancer properties of MSCs are –typically- determined wi . . .th respect to type and concentrations of soluble molecules found in their physiological environment. In mammals the immune system protects the organism -not only- from certain microorganisms, but also from any entity that it recognizes as foreign, including its own cells when it is received as a threat. This protection can sometimes occur by increasing the number of immune cells and sometimes by suppressing a pathologically hyper-induced immunological response. In particular, realization of the bi-directional effect of MSCs on immune cells has placed substantial emphasis on this area of research. This chapter focuses on the interaction of MSCs with the immune cells, the bilateral role of these interactions, and whether studies that aim to understand these interactions can yield promising results in terms of developing improved use of MSCs in treatment. © Springer International Publishing AG, part of Springer Nature 2018 Daha fazlası Daha az

Cytoglobin inhibits migration through PI3K/AKT/mTOR pathway in fibroblast cells

Demirci, S. | Doğan, A. | Apdik, H. | Tuysuz, E.C. | Gulluoglu, S. | Bayrak, O.F. | Şahin, Fikrettin

Article | 2018 | Molecular and Cellular Biochemistry437 ( 01.02.2020 ) , pp.133 - 142

Cell proliferation and migration are crucial in many physiological processes including development, cancer, tissue repair, and wound healing. Cell migration is regulated by several signaling molecules. Identification of genes related to cell migration is required to understand molecular mechanism of non-healing chronic wounds which is a major concern in clinics. In the current study, the role of cytoglobin (CYGB) gene in fıbroblast cell migration and proliferation was described. L929 mouse fibroblast cells were transduced with lentiviral particles for CYGB and GFP, and analyzed for cell proliferation and migration ability. Fibroblas . . .t cells overexpressing CYGB displayed decreased cell proliferation, colony formation capacity, and cell migration. Phosphorylation levels of mTOR and two downstream effectors S6 and 4E-BP1 which take part in PI3K/AKT/mTOR signaling declined in CYGB-overexpressing cells. Microarray analysis indicated that CYGB overexpression leads to downregulation of cell proliferation, migration, and tumor growth associated genes in L929 cell line. This study demonstrated the role of CYGB in fibroblast cell motility and proliferation. CYGB could be a promising candidate for further studies as a potential target for diseases related to cell migration such as cancer and chronic wound treatment. © 2017, Springer Science+Business Media, LLC Daha fazlası Daha az

Evidence for an association of serum melatonin concentrations with recognition and circadian preferences in patients with schizophrenia

Sahbaz, C. | Özer, O.F. | Kurtulmus, A. | Kırpınar, I. | Şahin, Fikrettin | Guloksuz, S.

Article | 2019 | Metabolic Brain Disease34 ( 3 ) , pp.865 - 874

Melatonin, a neuro-differentiation factor, may play a role in the neurodevelopmental origins of schizophrenia. Cognitive impairment and decreased melatonin are reported in schizophrenia; however, the relationship between them remains unclear. We hypothesised that patients with schizophrenia would have lower concentrations of circulating melatonin than healthy controls and that melatonin levels would be associated with cognitive impairment. This study included 47 patients with schizophrenia and 40 healthy controls (HC). Serum melatonin concentrations were measured using the enzyme-linked immunosorbent assay. Positive and Negative Syn . . .drome Scales (PANSS), The Morningness-Eveningness Questionnaire (MEQ), Pittsburgh Sleep Quality Index (PSQI), the Stroop and Oktem verbal memory processes (VMPT) tests were applied. Patients with schizophrenia had lower levels of melatonin compared to the HC group (p = 0.016), also after controlling for age, sex, and body mass index (BMI) (p = 0.024). In patients with schizophrenia, melatonin concentrations were associated with higher BMI (rho = 0.34, p = 0.01) and lower MEQ score (rho = -0.29, p = 0.035). The patient sample was split into low and high melatonin categories by using the median melatonin concentration in HC as the cut-off. Patients in the low melatonin group had poorer performance in VMPT-Recognition (p = 0.026) and Stroop-Colour Error (p = 0.032). Notwithstanding its limitations, the findings of this exploratory study suggest that decreased serum melatonin concentrations observed in schizophrenia might also be associated with cognitive impairment and circadian preferences. Future studies are required to investigate the role of melatonergic pathways in patients with schizophrenia. © 2019, Springer Science+Business Media, LLC, part of Springer Nature Daha fazlası Daha az

Enterobacter Strains Might Promote Colon Cancer

Yurdakul, D. | Yazgan-Karataş, A. | Şahin, Fikrettin

Article | 2015 | Current Microbiology71 ( 3 ) , pp.403 - 411

Many studies have been performed to determine the interaction between bacterial species and cancer. However, there has been no attempts to demonstrate a possible relationship between Enterobacter spp. and colon cancer so far. Therefore, in the present study, it is aimed to investigate the effects of Enterobacter strains on colon cancer. Bacterial proteins were isolated from 11 Enterobacter spp., one Morganella morganii, and one Escherichia coli strains, and applied onto NCM460 (Incell) and CRL1790 (ATCC) cell lines. Cell viability and proliferation were determined in MTS assay. Flow Cytometry was used to detect CD24 level and apopto . . .sis. Real-Time PCR studies were performed to determine NFKB and Bcl2 expression. Graphpad Software was used for statistical analysis. The results showed that proteins, isolated from the Enterobacter spp., have significantly increased cell viability and proliferation, while decreasing the apoptosis of the cell lines tested. The data in the present study indicated that Enterobacter strains might promote colon cancer. Moreover, Enterobacter spp. could be a clinically important factor for colon cancer initiation and progression. Studies can be extended on animal models in order to develop new strategies for treatment. © 2015, Springer Science+Business Media New York Daha fazlası Daha az

Boron promotes streptozotocin-induced diabetic wound healing: roles in cell proliferation and migration, growth factor expression, and inflammation

Demirci, S. | Doğan, A. | Aydın, S. | Dülger, E.Ç. | Şahin, Fikrettin

Article | 2016 | Molecular and Cellular Biochemistry417 ( 01.02.2020 ) , pp.119 - 133

Acute wounds do not generally require professional treatment modalities and heal in a predictable fashion, but chronic wounds are mainly accompanied with infection and prolonged inflammation, leading to healing impairments and continuous tissue degradation. Although a vast amount of products have been introduced in the market, claiming to provide a better optimization of local and systemic conditions of patients, they do not meet the expectations due to being expensive and not easily accessible, requiring wound care facilities, having patient-specific response, low efficiency, and severe side-effects. In this sense, developing new, . . .safe, self-applicable, effective, and cheap wound care products with broad-range antimicrobial activity is still an attractive area of international research. In the present work, boron derivatives [boric acid and sodium pentaborate pentahydrate (NaB)] were evaluated for their antimicrobial activity, proliferation, migratory, angiogenesis, gene, and growth factor expression promoting effects on dermal cells in vitro. In addition, boron-containing hydrogel formulation was examined for its wound healing promoting potential using full-thickness wound model in streptozotocin-induced diabetic rats. The results revealed that while both boron compounds significantly increased proliferation, migration, vital growth factor, and gene expression levels of dermal cells along with displaying remarkable antimicrobial effects against bacteria, yeast, and fungi, NaB displayed greater antimicrobial properties as well as gene and growth factor expression inductive effects. Animal studies proved that NaB-containing gel formulation enhanced wound healing rate of diabetic animals and histopathological scores. Overall data suggest a potential promising therapeutic option for the management of chronic wounds but further studies are highly warranted to determine signaling pathways and target metabolisms in which boron is involved to elucidate the limitations and extend its use in clinics. © 2016, Springer Science+Business Media New York Daha fazlası Daha az

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