Novel Cell-Based Therapies in Hepatic Disorders

In the recent decade, liver diseases with high mortality rate have became one of the major health problems worldwide. Liver transplantation is the most effective and the standard treatment for decompensated liver disease, but, shortage of available organs and inaccuracy in modeling of the liver diseases are the most limiting issues in treatment. Regenerative medicine and cell based therapy strategies have provided promising results through cooperating in natural liver regeneration ability or providing liver function support as a bridge before transplantation. Induction of differentiation in different types of stem cells such as embryonic, induced pluripotent stem cells, mesenchymal and hematopoietic stem cells are the most common methods that provide a functional population of hepatocytes to be used in diseases like cirrhosis, cancer and all types of fatty liver diseases, and significantly restore the normal levels of hepatic factors. In addition, mesenchymal and hematopoietic stem cells improve the symptoms of autoimmune diseases by modulatation of immune responces and reduction of inflammation. Other cell treatment strategies are isolating the patient's own hepatocytes in the lab, in vito correction of defected genes and transplanting them back to the patient that can improve the symptoms of genetic disorders. In this study, we first reviewed the basic concepts related to liver diseases, then highlighted the most recent advances in cell-based therapies and regenerative medicine for the treatment of liver disease, along with tissue engineering and bio-artificial liver devices

Antibacterial properties of nanoporous graphene oxide/cobalt metal organic framework

Metal-organic framework (MOF) based graphene oxide (GO) recently merits of attention because of the relative correspondence of GO with metal ions and organic binding linkers. Furthermore, introducing the GO to the Co-MOF to make a new nanoporous hybrid have are improved the selectivity and stability of the Co-MOF. Here the graphene oxide/cobalt metal organic framework (GO/Co-MOF) was synthesized by a solvothermal process using cobalt salt and terephthalic acid and used for biocidal activity, against the growth of the Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus bacteria. X-ray diffraction, Fourier transform infrared spectroscopy and Raman spectroscopy were confirmed the successful synthesize of metal organic framework and incorporation of Co-MOF in to GO sheets. Scanning electron microscopy was showed the cornflower structure of GO/Co-MOF, and transmission electron microscopy was confirmed, the Co-MOF are decorated on GO. Cytotoxicity study of GO/Co-MOF using 3-[4,5-dimethylthiazol-2yl]-2,5-diphenyltetrazolium bromide (MTT) cell viability assay showed the biocompatibility to human fibroblasts cell over 72 h. The growth inhibition of the Escherichia coli and Staphylococcus aureus bacteria are reached over 99% for bacteria concentration of 100 mu g/mL. The excellent antibacterial activity of GO based Co-MOF is linked to synergistic effect of sharp edges of the GO sheets and the toxic effect of cobalt ions (Co2+) which are released from their surfaces. The GO/Co-MOF radical scavenging assay was measured using 1,1-diphenyl-2-picrylhydrazyl (DPPH) antioxidant assay for samples incubated with cells which confirmed the minimum radicals' toxicity on bacteria. This novel graphene oxide based MOF with its intrinsic superior porous structure, highly active metal coordination, and commercial linker, is an excellent promising candidate to use in biological and pharmaceutical applications as high potential sustained bactericidal materials

Conjugated Linoleic Acid Treatment Attenuates Cancerous features in Hepatocellular Carcinoma Cells.

BACKGROUND: A growing number of hepatocellular carcinoma (HCC), and recurrence frequency recently have drawn researchers' attention to alternative approaches. The concept of differentiation therapies (DT) relies on inducing differentiation in HCC cells in order to inhibit recurrence and metastasis. Hepatocyte nuclear factor 4 alpha (HNF4α) is the key hepatogenesis transcription factor and its upregulation may decrease the invasiveness of cancerous cells by suppressing epithelial-mesenchymal transition (EMT). This study aimed to evaluate the effect of conjugated linoleic acid (CLA) treatment, natural ligand of HNF4α, on the proliferation, migration, and invasion capacities of HCC cells in vitro. Materials and Method. Sk-Hep-1 and Hep-3B cells were treated with different doses of CLA or BIM5078 [1-(2'-chloro-5'-nitrobenzenesulfonyl)-2-methylbenzimidazole], an HNF4α antagonist. The expression levels of HNF4a and EMT related genes were evaluated and associated to hepatocytic functionalities, migration, and colony formation capacities, as well as to viability and proliferation rate of HCC cells. RESULTS: In both HCC lines, CLA treatment induced HNF4α expression in parallel to significantly decreased EMT marker levels, migration, colony formation capacity, and proliferation rate, whereas BIM5078 treatment resulted in the opposite effects. Moreover, CLA supplementation also upregulated ALB, ZO1, and HNF4α proteins as well as glycogen storage capacity in the treated HCC cells. CONCLUSION: CLA treatment can induce a remarkable hepatocytic differentiation in HCC cells and attenuates cancerous features. This could be as a result of HNF4a induction and EMT inhibition