Role of macrophages in pathomorphogenesis of alcoholic liver disease

Alcoholic liver disease combines various structural and functional impairments of liver caused by excessive alcohol consumption. Alcohol, as a direct hepatotoxic agent, is metabolized in the liver and affects both resident cells and their microenvironment. These changes are reflected in the resulting imbalance of pro- and anti-inflammatory mediators synthesized by the liver macrophages. To date, it is known about the polarization and phenotypic diversity of this cell population, and about macrophages and monocytes involvement in the development of alcoholic hepatitis. These facts allow us to consider macrophages as potential therapeutic targets. However, the available data do not fully disclose the mechanisms of inter- and intradifferon interactions in the human body. The review discusses the results of current studies on the involvement of liver macrophages in the pathomorphogenesis of alcoholic liver disease and the potential for their use in the treatment of this disease

Caroli syndrome: a clinical case with detailed histopathological analysis

© 2018, Japanese Society of Gastroenterology. Herein we present a clinical case of the Caroli syndrome caused by the compound heterozygous mutation in the PKHD1 gene. Histopathological assessment of liver detected biliary cirrhosis, numerous dilated bile ducts of various sizes, hyperplastic cholangiocytes containing a large amount of acid mucopolysaccharides, decreased ß-tubulin expression and increased proliferation of cholangiocytes. A significant proportion of hepatic tissue was composed of giant cysts lined with a single layer of cholangiocytes, containing pus and bile in its lumen and surrounded by granulation tissue. An accumulation of neutrophils in the lumen of the bile ducts was observed, as well as an infiltration of the ducts and cysts surrounding connective tissue by CD4+ and to a lesser extent CD8+ lymphocytes. This may be caused by the expression of HLA-DR by cholangiocytes. Atrophy and desquamation of the epithelium of collecting tubules with the formation of microcysts were detected in the kidneys without a clinically significant loss of renal function. Morphopathogenetic mechanisms of the Caroli syndrome can be targets for a potential pathogenetic therapy and prevention of its manifestations and complications

Characterization of rat myofibroblasts isolated from liver portal tracts using explantation technique

Today there is no effective approach to treat liver fibrosis and the only way is transplantation of donors' liver. Investigation of molecular-cellular mechanisms of liver fibrosis can help to discover new ways of slowing down or even reverse the process of fibrogenesis in liver. For a long time hepatic stellate cells were undeservingly blamed for being the major causer of liver fibrosis, because they were considered as the main source of myofibroblasts, that synthesize connective tissue extracellular matrix. In this particular work explantation approach was used to isolate cell culture from portal tracts. It was shown that received cells are portal fibroblasts, and, just as hepatic stellate cells, in case of liver alteration can differentiate in myofibroblasts, that express α-smooth muscle actin. During long-term cultivation it was shown that portal myofibroblasts can differentiate into fibroblasts and back on late passages. So, we can conclude, that there is a potency to reverse the process of fibrogenesis in liver. © Human stem cells institute, 2013

Genetically modified human umbilical cord blood mononuclear cells as potential stimulators of neuroregeneration in degenerative disorders of central nervous system

Gene-cell therapy is a new step for the treatment of different human disorders including central nervous system degenerative diseases. In this review we focused on the last challenges in the field of human umbilical cord blood mononuclear cells transplantation - An attempt to support neuronal cells survival and to stimulate the neuroregeneration. As a potential therapy for the treatment of neurodegenerative diseases we reviewed the latest advances in gene modification of human umbilical cord blood mononuclear cells as a novel tool for the effective delivery of neuroprotective factors and growth factors in the injured or degenerative areas of the central nervous system under pathological conditions. The main topic of this review is the potential therapy of the amyotrophic lateral sclerosis - The progressive neurodegenerative disorder affecting primarily upper and lower motoneurons - by using genetically modified human umbilical cord blood mononuclear cells. The results from the up-to-date experiments indicated the opportunity to obtain differentiated macrophages, endothelial cells, or astrocytes from the genetically modified human umbilical cord blood mononuclear cells after their transplantation in the mouse model of the amyotrophic lateral sclerosis. Taken together, these data build the high-capacity platform for the supporting of degenerating neurons, structural and functional recovery of the brain and spinal cord after trauma, ischemia and other neurodegenerative disorders. © Human stem cells institute, 2013

Considerations and strategies in L2 vocabulary acquisition among Japanese 1st year university students.

This article proposes a framework of strategies1） for L2 vocabulary acquisition among low-to-mid level L2 learners in their first year at Kansai University. The framework relies upon considerations posited by Kudo (1999), as well as, Hunt and Beglar’s (2005) model for developing EFL reading vocabulary, although the objective for our target learners is tofacilitate vocabulary acquisition in a learner-centered communicative context, where possible. This paper firstly underlines the critical role of vocabulary in second language acquisition, while raising awareness of the surrounding pedagogic climate in Japanese secondary education.研究ノー

Gene therapy using plasmid DNA encoding vascular endothelial growth factor 164 and fibroblast growth factor 2 genes for the treatment of horse tendinitis and desmitis: Case reports

© 2017 Kovac, Litvin, Aliev, Zakirova, Rutland, Kiyasov and Rizvanov. In this clinical study, for the first time we used the direct gene therapy to restore severe injuries of the suspensory ligament branch and superficial digital flexor tendon in horses (Equus caballus). We injected the plasmid DNA encoding two therapeutic species-specific growth factors: vascular endothelial growth factor 164 and fibroblast growth factor 2 at the site of injury in the suspensory ligament branch and tendon. Treatment effects were evaluated with the use of clinical observation and ultrasound imaging during a period of a few months. We showed that gene therapy used within a period of 2-3 months after the injury resulted in the complete recovery of functions and full restoration of the severely damaged suspensory ligament and superficial digital flexor tendon

Interaction and self-organization of human mesenchymal stem cells and neuro-blastoma SH-SY5Y cells under co-culture conditions: A novel system for modeling cancer cell micro-environment

The common drawback of many in vitro cell culture systems is the absence of appropriate micro-environment, which is formed by the combination of factors such as cell-cell contacts, extracellular matrix and paracrine regulation. Micro-environmental factors in a tumor tissue can influence physiological status of the cancer cells and their susceptibility to anticancer therapies. Interaction of cancer cells with their micro-environment and regional stem cells, therefore, is of particular interest. Development of in vitro systems which allow more accurate modeling of complex relations occurring in real tumor environments can increase efficiency of preclinical assays for screening anticancer drugs. The aim of this work was to study interactions between human mesenchymal stem cells (MSCs) and neuro-blastoma cancer SH-SY5Y cells under co-culture conditions on different coated surfaces to determine the effect of co-existence of cancer and stem cells on each cellular population under various stress conditions. We developed an efficient in vitro system for studying individual cancer and stem cell populations during co-culture using differential live fluorescent membrane labeling, and demonstrated self-organization of cancer and stem cells during co-culture on various coated surfaces. Our findings support the evidence that cancer and stem cell interactions play important roles in cellular behavior of cancer cells. These properties can be used in different fields of cancer research, tissue engineering and biotechnology. © 2010 Elsevier B.V

A direct technique for magnetic functionalization of living human cells

Functionalized living cells are regarded as effective tools in directed cell delivery and tissue engineering. Here we report the facile functionalization of viable isolated HeLa cells with superparamagnetic cationic nanoparticles via a single-step biocompatible process. Nanoparticles are localized on the cellular membranes and do not penetrate into the cytoplasm. The magnetically responsive cells are viable and able to colonize and grow on substrates. Magnetically facilitated microorganization of functionalized cells into viable living clusters is demonstrated. We believe that the technique described here may find a number of potential applications in cell-based therapies and in development of whole-cell biosensors. © 2011 American Chemical Society

Histopathological Analysis of Skeletal Muscle Biopsy of Patient with Peripheral Arterial Disease before and after Peripheral Blood Stem Cells Intramuscular Injection

© 2016, Springer Science+Business Media New York.Peripheral arterial diseases are characterized by a progressing tissue ischemia which results in the invalidization of patients. The aim of our research was to study the morphological effects of autologous peripheral blood stem cells intramuscular injection into patients with peripheral arterial disease. Peripheral blood stem cells were transplanted intramuscularly into a 48-year-old male patient with peripheral arterial disease stage IIb by Fontaine. The biopsies of his gastrocnemius muscle were taken before the stem cells were transplanted and 3 months after transplantation. These biopsies were stained with H&E and also with antibodies against CD34, myogenin, caspase 3, and bcl-2. Immunohistochemical study results showed an increase of capillary density of 32.7 % (P = 0.005). In muscular biopsies obtained before therapy, we identified single myogenin+ myosatellite cells, while 3 months after transplantation we detected the presence of cells with myogenin-positive nuclei and multinucleated myotubes. We also observed the formation of young myogenin+ muscle fibers with central nuclei. There was no significant difference in the expression of caspase-3 before transplantation and 3 months after transplantation. An increased number of bcl-2+ myosatellite cells, myotubes, and muscle fibers were detected after transplantation. The patient’s ankle-brachial index increased by 13.56 % (0.59 before and 0.67 3 months post transplantation). The patient’s pain-free walking distance by 89.97 % (from 59.56 to 113.77 m). Control arteriograms showed the formation of new collaterals. Transplanted autologous peripheral blood stem cells stimulated the formation of new capillaries, the activation of myosatellite cells and bcl-2 expression in muscle fibers

Human tooth germ stem cells preserve neuro-protective effects after long-term cryo-preservation

The use of mesenchymal stem cells (MSCs) has been shown to be promising in chronic disorders such as diabetes, Alzheimer's dementia, Parkinson's disease, spinal cord injury and brain ischemia. Recent studies revealed that human tooth germs (hTG) contain MSCs which can be easily isolated, expanded and cryo-preserved. In this report, we isolated human tooth germ stem cells (hTGSCs) with MSC characteristics from third molar tooth germs, cryo-preserved them at -80°C for 6 months, and evaluated for their surface antigens, expression of pluri-potency associated genes, differentiation capacity, karyotype, and proliferation rate. These characteristics were compared to their non-frozen counterparts. In addition, neuro-protective effects of cryo-preserved cells on neuro-blastoma SH-SY5Y cells were also assessed after exposure to stress conditions induced by hydrogen-peroxide (oxidative stress) and paclitaxel (microtubule stabilizing mitotic inhibitor). After long term cryo-preservation hTGSCs expressed surface antigens CD29, CD73, CD90, CD105, and CD166, but not CD34, CD45 or CD133, which was typical for non-frozen hTGSCs. Cryo-preserved hTGSCs were able to differentiate into osteo-, adipo- and neuro-genic cells. They also showed normal karyotype after high number of population doublings and unchanged proliferation rate. On the other hand, cryo-preserved cells demonstrated a tendency for lower level of pluri-potency associated gene expression (nanog, oct4, sox2, klf4, c-myc) than non-frozen hTGSCs. hTGSCs conditioned media increased survival of SH-SY5Y cells exposed to oxidative stress or paclitaxel. These findings confirm that hTGSCs preserve their major characteristics and exert neuro-protection after long-term cryopreservation, suggesting that hTGSCs, harvested from young individuals and stored for possible use later as they grow old, might be employed in cellular therapy of age-related degenerative disorders. © Bentham Science Publishers Ltd