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Öğe Combination therapy using nanomaterials and stem cells to treat spinal cord injuries(Elsevier Science, 2022) Zarepour, Arezou; Bal Öztürk, Ayça; Koyuncu Irmak, Duygu; Yaşayan, Gökçen; Gökmen, Aylin; Karaöz, Erdal; Zarepour, Atefeh; Zarrabi, Ali; Mostafavi, EbrahimAs a part of the central nervous system, the spinal cord (SC) provides most of the communications between the brain and other parts of the body. Any damage to SC interrupts this communication, leading to serious problems, which may remain for the rest of their life. Due to its significant impact on patients’ quality of life and its exorbitant medical costs, SC injury (SCI) is known as one of the most challengeable diseases in the world. Thus, it is critical to introduce highly translatable therapeutic platforms for SCI treatment. So far, different strategies have been introduced, among which utilizing various types of stem cells is one of the most interesting ones. The capability of stem cells to differentiate into several types of cell lines makes them promising candidates for the regeneration of injured tissues. One of the other interesting and novel strategies for SCI treatment is the appli- cation of nanomaterials, which could appear as a carrier for therapeutic agents or as a platform for culturing the cells. Combining these two approaches, stem cells and nanomaterials, could provide promising therapeutic strategies for SCI management. Accordingly, in this review we have summarized some of the recent advance- ments in which the applications of different types of stem cells and nanomaterials, alone and in combination forms, were evaluated for SCI treatment.Öğe Generation of induced pluripotent stem cells from human bone marrow-derived mesenchymal stem cells(Springer Link, 2021) Koyuncu Irmak, Duygu; Karaöz, ErdalAdult somatic cells can be reprogrammed and become pluripotent called induced pluripotent stem cells (iPSC) when they are induced by the stemness genes. The iPSCs have been representing a research and development platform for cell-based therapies, and even in gene editing technologies as they provide the ability to differentiate almost all cell types. The efficiency of the protocols for the iPSC development defines the success of the experiments' outcome. Here, we describe the optimized protocol for obtaining human iPSCs derived from mesenchymal stem cells of bone-marrow origin to shed a light on the hurdles in the research laboratories.Öğe Mesenchymal stem cells for the treatment of covid-19: why and when they should be used?(Nova Science Publishers, 2021) Darıcı, Hakan; Sun, Eda; Koyuncu Irmak, Duygu; Karaöz, ErdalCOVID-19 is a pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which caused deaths of more than 300.000 people around the world within the first few months of 2020. SARS-CoV-2 uses ACE2 receptors to infect respiratory system cells and may cause pneumonia and severe lung damage. The virus can also spread other organs rapidly via ACE2 expressing endothelial cells and cause coagulopathy, and further damage to the organs. Another and probably more harmful effect of the virus is the overreaction of the immune system leading to hyperinflammation causing multiple organ failure and death. Therefore COVID-19 can be considered as a viral infection causing auto-immune disorders. Currently, no vaccine or effective pharmacological treatment established for the disease. On the other hand, Mesenchymal Stem Cells (MSCs) possess anti-inflammatory and immune-regulatory effects along with their regenerative abilities. In this article, we thoroughly evaluate the COVID-19 pandemic and the damage mechanisms on the cellular level which can be ameliorated with the cellular therapies. We also gathered previous and ongoing stem cell clinical trial data from diseases with similar symptoms. All these accumulated data and current clinical trial results indicate that the cellular therapies could be the most effective treatment option for COVID-19 patients to ameliorate the damaged tissues and save lives.Öğe Performing the comparative analysis to understand the functional roles of genes in different pathways of cardiomyopathy disease(Elsevier, 2021) Atak, Evren; Karaoğlu, Dilara; Serttürk, Seda; Koyuncu Irmak, Duygu; Yenenler-Kutlu, AslıPersonalized medicine is one of the popular approaches in biological sciences. Due to the great attention in personalized medicine, there exists a need for health decision algorithms developed through high-level pro-gramming languages that already compromised the statistical analyses and numerical computations. Here, we present a tool that enables us to facilitate making research in the PubMed database by classifying the scientific literature from the published abstracts and then performed the comparative analysis to highlight the importance of gene-variant relationships in the decision steps. After retrieving related genes from literature, we performed pathway analysis with them by using computer-based tools to differentiate these sub-pathways in cardiomy-opathy disease that are listed as hypertrophic, dilated, and arrhythmogenic right ventricular cardiomyopathy. Then, the pathogenic variants existing in these genes at each sub-pathway are retrieved, and the mechanistic interpretation about them has been gained to explain more about the differences in genes’ mode of action. Lastly, the need of structure-based studies to explain the etiology of the disease has been emphasized by providing the protein structures of related genes as a guide. This study presents the importance of combining the text-mining approach with the bioinformatics tool in effective manner both for catching up with the updated literature and for revealing newly identified genes or pathways.Öğe Stem cell based therapy option in COVID-19: is it really promising?(INT SOC AGING & DISEASE, 2020) Koyuncu Irmak, Duygu; Darıcı, Hakan; Karaöz, ErdalThe COVID-19 patients were first detected in China, in December 2019, then the novel virus with associated pneumonia and other diseases spread quickly to worldwide becoming a serious public health intimidation. Despite all the efforts, the pharmacological agents used for controlling or treating the disease, especially respiratory problems, have not been accomplished so far. Among various treatment options, mesenchymal stem cell-based cellular therapies are being investigated, because of their regeneration ability and multipotency along with other features like immunomodulation, antifibrosis and anti- inflammatory effects. This paper intends to analyze the current clinical trials on stem cell treatment of novel virus, searching and reviewing the available information and the International Clinical Trials Registry Platform (ICTRP) of World Health Organization (WHO). We concluded that the stem cell treatment of COVID-19 is found promising with pilot studies' results, but still in the early development phase. There is an urgent need for large-scale investigations to confirm and validate the safety and efficacy profile of these therapies with reliable scientific evidence.Öğe The systematic effect of mesenchymal stem cell therapy in critical COVID-19 patients: a prospective double controlled trial(Sage Journals, 2021) Adaş, Gökhan; Çukurova, Zafer; Kart Yaşar, Kadriye; Yılmaz, Rabia; Işıksaçan, Nilgün; Kasapoğlu, P.; Yeşilbağ, Zuhal; Koyuncu Irmak, Duygu; Karaöz, ErdalThe aim of this clinical trial was to control the cytokine storm by administering mesenchymal stem cells (MSCs) to critically-ill COVID-19 patients, to evaluate the healing effect, and to systematically investigate how the treatment works. Patients with moderate and critical COVID-19 clinical manifestations were separated as Group 1 (moderate cases, n = 10, treated conventionally), Group 2 (critical cases, n = 10, treated conventionally), and Group 3 (critical cases, n = 10, treated conventionally plus MSCs transplantation therapy of three consecutive doses on treatment days 0, 3, and 6, (as 3 × 106 cells/kg, intravenously). The treatment mechanism of action was investigated with evaluation markers of the cytokine storm, via biochemical parameters, levels of proinflammatory and anti-inflammatory cytokines, analyses of tissue regeneration via the levels of growth factors, apoptosis markers, chemokines, matrix metalloproteinases, and granzyme-B, and by the assessment of the immunomodulatory effects via total oxidant/antioxidant status markers and the levels of lymphocyte subsets. In the assessment of the overall mortality rates of all the cases, six patients in Group-2 and three patients in Group-3 died, and there was no loss in Group-1. Proinflammatory cytokines IFN?, IL-6, IL-17A, IL-2, IL-12, anti-inflammatory cytokines IL-10, IL-13, IL-1ra, and growth factors TGF-?, VEGF, KGF, and NGF levels were found to be significant in Group-3. When Group-2 and Group-3 were compared, serum ferritin, fibrinogen and CRP levels in Group-3 had significantly decreased. CD45 +, CD3 +, CD4 +, CD8 +, CD19 +, HLA-DR +, and CD16 + / CD56 + levels were evaluated. In the statistical comparison of the groups, significance was only determined in respect of neutrophils. The results demonstrated the positive systematic and cellular effects of MSCs application on critically ill COVID-19 patients in a versatile way. This effect plays an important role in curing and reducing mortality in critically ill patients.Öğe The systematic effect of mesenchymal stem cell therapy in critical COVID-19 patients: a prospective double controlled trial(WILEY, 2021) Adaş, Gökhan; Işıksaçan, Nilgün; Atar, Pınar; Çukurova, Zafer; Yaşar, Kadriye Kart; Yılmaz, Rabia; Yeşilbağ, Zuhal; Koyuncu Irmak, Duygu; Karaöz, Erdal[No Abstract Available]
