Finally these results suggest that this biomimetic model with fibrin may provide a vastly applicable 3D culture system to study the effect of anti-cancer drugs such as atrovastatin on tumor malignancy in vitro and in vivo and atorvastatin could be used as anticancer agent for glioblastoma treatment.

Human endometrial stem cells (hEnSCs) are a new source of adult multipotent stem cells with the ability of differentiation into many cell lineages. Many stem cell sources are desirable for differentiation into Schwann cells. Schwann-like cells derived from hEnSCs may be one of the ideal alternative cell sources for Schwann cell generation. In this study, for differentiation of hEnSCs into Schwann cells, hEnSCs were induced with RA/FSK/PDGF-AA/HRG as an induction medium for 14 days. The cells were cultured in a tissue culture plate (TCP) and fibrin gel matrix. The viability of cultured cells in the fibrin gel and TCP was analyzed with 3-[4,5-dimethyl-2-thia-zolyl]-2, 5-diphenyl-2H-tetrazolium bromide (MTT) assay for 7 days. The attachment of cells was analyzed with SEM and DAPI staining. The expression of S100 and P75 as Schwann cell markers was evaluated by immunocytochemistry and quantitative real-time PCR (RT-PCR). The evaluation of the MTT assay and gene expression showed that the survival rate and differentiation of hEnSCs into Schwann cells in the fibrin gel were better than those in the TCP group. These results suggest that human EnSCs can be differentiated into Schwann cells in the fibrin gel better than in the TCP, and the fibrin gel might provide a suitable three-dimensional (3D) scaffold for clinical applications for cell therapy of the nervous system.

Glioblastoma multiform (GBM) is a primary malignant brain tumor with a few therapeutic targets available for it. The interaction between the immune system and glioma is an important factor that could lead to novel therapeutic approaches to fight glioma. In this study, we investigated in vitro anti-inflammatory and apoptotic activity of atorvastatin in different concentrations 1, 5, and 10 μM on glioma spheroid cells cultured in a three-dimensional model in fibrin gel that indicate the complex in vivo microenvironment better than a simple two-dimensional cell culture. A mechanistic insight into the role of IL-17RA, TRAF3IP2, and apoptotic genes in progression of glioma could provide an important way for therapy of malignant tumors with manipulation of this inflammatory axis. To reach for these aims, after 24 and 48 h exposure with different concentrations of atorvastatin, caspase-8, caspase-3, Bcl-2, TRAF3IP2, and IL-17RA gene expression were assayed. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay and cell cycle assay were used for evaluating the cell apoptosis and proliferation. The results showed that atorvastatin has anti-inflammatory and apoptotic effects against glioma spheroids. Atorvastatin induced the expression of caspase-3 and caspase-8 and downregulated the expression of Bcl-2, TRAF3IP2, and IL-17RA especially at 10 μM concentration. These effects are dose dependent. The most likely mechanisms are the inhibition of inflammation by IL-17RA interaction with TRAF3IP2 and NF-κB signaling pathway. Finally, these results suggest that atorvastatin could be used as an anti-cancer agent for glioblastoma treatment.

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