Current Issue : April - June Volume : 2015 Issue Number : 2 Articles : 5 Articles
Background: Chronic obstructive pulmonary disease presents with two different phenotypes: chronic bronchitis\nand emphysema with parenchymal destruction. Decreased expression of vascular endothelial growth factor and\nincreased endothelial cell apoptosis are considered major factors for emphysema. Stem cells have the ability of\nvascular regeneration and function as a repair mechanism for the damaged endothelial cells. Currently, minimally\ninvasive interventional procedures such as placement of valves, bio-foam or coils are performed in order to improve\nthe disturbed mechanical function in emphysema patients. However, these procedures cannot restore functional\nlung tissue. Additionally stem cell instillation into the parenchyma has been used in clinical studies aiming to\nimprove overall respiratory function and quality of life.\nMethods: In our current experiment we induced emphysema with a DDMC non-viral vector in BALBC mice and\nsimultaneously instilled stem cells testing the hyposthesis that they might have a protective role against the\ndevelopment of emphysema. The mice were divided into four groups: a) control, b) 50.000 cells, c) 75.000 and\nd) 100.000 cells.\nResults: Lung pathological findings revealed that all treatment groups had less damage compared to the control\ngroup. Additionally, we observed that emphysema lesions were less around vessels in an area of 10 ?m.\nConclusions: Our findings indicate that stem cell instillation can have a regenerative role if applied upon a tissue\nscaffold with vessel around.\nVirtual Slides: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/\nvs/13000_2014_195...
Background: Mesenchymal stromal cells (MSC) can be obtained from potentially any tissue from the human body,\nbut cells purified from different sources are undoubtedly different, and for each medical application, the MSC with\nthe best regenerative potential should be chosen.\nResults: Bone marrow-derived mesenchymal stromal cells (BM-MSC), adipose tissue-derived mesenchymal stromal\ncells (AT-MSC) and Wharton�s Jelly-derived mesenchymal stromal cells (WJ-MSC) were isolated from human tissues\nand were cultured under differentiation media supplemented with fetal bovine serum. We quantified the expression\nof stem cell and adipocyte genetic markers using quantitative real time PCR, as well as the secretion of cytokines,\nextracellular matrix components and growth factors using Luminex and ELISA. All three MSC differentiated into adipogenic\ncells. AT-MSC showed the highest shift in ADIPOQ, CEBPA and PPARG mRNA expression. BM-MSC kept high\nexpression levels of stem-cell markers SOX2 and POU5F1. WJ-MSC showed the lowest increase in mRNA expression\nwhen cells were induced to differentiate into adipocytes. Regarding protein secretion, adipocyte-like cells generated\nfrom WJ-MSC secreted the highest chemokine levels. AT-MSC-derived adipocyte-like cells secreted the lowest cytokine\namounts and the highest quantity of collagen types I and III. Adipocyte-like cells obtained from BM-MSC secreted\nhigh amounts of most angiogenic factors, growth factors TGF-?1 and TGF-?2, collagens type II and IV,\nheparan sulfate, laminin and aggrecan.\nConclusion: Mesenchymal stromal cells purified from different tissues have a different behavior when induced to\ndifferentiate into adipocyte-like cells....
Advancements in human genomics over the last two decades have shown that cancer is mediated by somatic\naberration in the host genome. This discovery has incited enthusiasm among cancer researchers; many now use\ntherapeutic approaches in genetic manipulation to improve cancer regression and find a potential cure for the\ndisease. Such gene therapy includes transferring genetic material into a host cell through viral (or bacterial) and\nnon-viral vectors, immunomodulation of tumor cells or the host immune system, and manipulation of the tumor\nmicroenvironment, to reduce tumor vasculature or to increase tumor antigenicity for better recognition by the\nhost immune system. Overall, modest success has been achieved with relatively minimal side effects. Previous\napproaches to cancer treatment, such as retrovirus integration into the host genome with the risk of mutagenesis\nand second malignancies, immunogenicity against the virus and/or tumor, and resistance to treatment with disease\nrelapse, have markedly decreased with the new generation of viral and non-viral vectors. Several tumor-specific\nantibodies and genetically modified immune cells and vaccines have been developed, yet few are presently\ncommercially available, while many others are still ongoing in clinical trials. It is anticipated that gene therapy will\nplay an important role in future cancer therapy as part of a multimodality treatment, in combination with, or\nfollowing other forms of cancer therapy, such as surgery, radiation and chemotherapy. The type and mode of gene\ntherapy will be determined based on an individual�s genomic constituents, as well as his or her tumor specifics,\ngenetics, and host immune status, to design a multimodality treatment that is unique to each individual�s specific\nneeds....
Glioblastoma multiforme (GBM) is the most frequent and devastating primary brain tumor in adults. Despite current\ntreatment modalities, such as surgical resection followed by chemotherapy and radiotherapy, only modest\nimprovements in median survival have been achieved. Frequent recurrence and invasiveness of GBM are likely due\nto the resistance of glioma stem cells to conventional treatments; therefore, novel alternative treatment strategies\nare desperately needed. Recent advancements in molecular biology and gene technology have provided attractive\nnovel treatment possibilities for patients with GBM. Gene therapy is defined as a technology that aims to modify\nthe genetic complement of cells to obtain therapeutic benefit. To date, gene therapy for the treatment of GBM has\ndemonstrated anti-tumor efficacy in pre-clinical studies and promising safety profiles in clinical studies. However,\nwhile this approach is obviously promising, concerns still exist regarding issues associated with transduction\nefficiency, viral delivery, the pathologic response of the brain, and treatment efficacy. Tumor development and\nprogression involve alterations in a wide spectrum of genes, therefore a variety of gene therapy approaches for\nGBM have been proposed. Improved viral vectors are being evaluated, and the potential use of gene therapy alone\nor in synergy with other treatments against GBM are being studied. In this review, we will discuss the most\ncommonly studied gene therapy approaches for the treatment of GBM in preclinical and clinical studies including:\nprodrug/suicide gene therapy; oncolytic gene therapy; cytokine mediated gene therapy; and tumor suppressor\ngene therapy. In addition, we review the principles and mechanisms of current gene therapy strategies as well as\nadvantages and disadvantages of each....
Background: Human hepatoma HepG2 cells are used as an in vitro model of the human liver. High-throughput\ntranscriptomic sequencing is an advanced approach for assessing the functional state of a tissue or cell type. However,\nthe influence of experimental factors, such as the sample preparation method and inter-laboratory variation, on the\ntranscriptomic profile has not been evaluated.\nResults: The whole-transcriptome sequencing of HepG2 cells was performed using the SOLiD platform and validated\nusing droplet digital PCR. The gene expression profile was compared to the results obtained with the same sequencing\nmethod in another laboratory and using another sample preparation method. We also compared the transcriptomic\nprofile HepG2 cells with that of liver tissue. Comparison of the gene expression profiles between the HepG2 cell line\nand liver tissue revealed the highest variation, followed by HepG2 cells submitted to two different sample preparation\nprotocols. The lowest variation was observed between HepG2 cells prepared by two different laboratories using the\nsame protocol. The enrichment analysis of the genes that were differentially expressed between HepG2 cells and liver\ntissue mainly revealed the cancer-associated gene signature of HepG2 cells and the activation of the response to\nchemical stimuli in the liver tissue. The HepG2 transcriptome obtained with the SOLiD platform was highly correlated\nwith the published transcriptome obtained with the Illumina and Helicos platforms, with moderate correspondence\nto microarrays.\nConclusions: In the present study, we assessed the influence of experimental factors on the HepG2 transcriptome and\nidentified differences in gene expression between the HepG2 cell line and liver cells. These findings will facilitate robust\nexperimental design in the fields of pharmacology and toxicology. Our results were supported by a comparative\nanalysis with previous HepG2 gene expression studies....
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