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Background:Schwann cells (SCs) can provide a suitable option for treatment not only diseases of peripheral nervous system (PNS), but also diseases of central nervous system (CNS). It is difficult to obtain sufficient large number of SCs for clinical purpose because of their restricted mitotic activity, and by sacrificing one or more functioning nerves with the consequence of loss of sensation. So, providing an alternative source for transplantation is desired. The aim of this study was isolation, characterization of human adipose derived stem cells (ADSCs), and transdifferentiation into Schwann-cells.Materials and Methods:After isolation of ADSCs by mechanical and enzymatic digestion of adipose samples, characterization human ADSCs using flow cytometry was carried out. Human ADSCs were sequentially treated with various factors for neurosphere formation and terminal differentiation into Schwann-like cells. We used Schwann cell markers, GFAP and S100 to confirm the effectiveness of the differentiation of human ADSCs using Immunostaining and real time RT-PCR techniques.Results:Flow cytometry analysis of ADSC showed isolated stem cells were positive for CD90 and CD44 markers of mesenchymal stem cells, but for CD45 and CD34 markers were negative. Dual immunofluorescence staining and real time RT-PCR analysis for GFAP and S100 markers were revealed that approximately 90% of differentiated cells expressed co-markers.Conclusion:We indicated that human ADSCs have a suitable option to induce Schwann-like cells for autologous transplantation, offer promise for treatment in demyelinating diseases.

The Schwann cells (SCs) may be obtain from nerve biopsies for autologous transplantation. However, it is difficult to obtain sufficient amount of SCs for clinical applications. Human adipose-derived stem cells (ADSCs) can be induced to differentiate into Schwann-like cells (S-like cells) and used for autologous transplantation. However, effect of leukemia inhibitory factor (LIF) on the myelinogenic ability of SC-like cells induced from human ADSC is not investigated yet. The aim of this study was to evaluate of the effect of exogenous LIF on myelinogenic potential of differentiated cells in vitro. ADSCs were harvested from human fat tissue and characterized using flow cytometry. Human ADSCs were treated for sphere formation and LIF was added to terminal differentiation medium. GFAP/S100β and MBP markers were used to confirm differentiation of human ADSCs, and myelinogenic ability of SC-like cells, respectively, using both immunostaining and real-time RT-PCR analysis. The analysis for GFAP(+)/S100β(+) revealed that LIF can increase both differentiated cells rates and the percentage of myelinating SC-like cells (p < 0.05). Our data showed that SC-like cells induced from human ADSCs were able to generate myelin when exposed to LIF and these cells could be a potential source for the treatment of peripheral and central axonal injuries.

BackgroundTRAIL and IFNγ are promising anti-cancer cytokines and it has been shown that IFNγ may sensitize cancer cells to TRAIL. Adipose derived mesenchymal stem cells (ADSCs) are attractive vehicles for delivering anti-cancer agents. In this study, we evaluated the therapeutic potential of PhiC31 (φC31) recombinase and/or piggyBac transposase (pBt) modified ADSCs expressing either TRAIL, IFNγ, or co-expressing TRAIL/IFNγ in mouse models of melanoma.MethodsThe expression and bioactivity of mouse IFNγ and TRAIL in φC31 and pBt modified cells were confirmed. We examined the effects of modified ADSCs on signal intensity of red fluorescence protein expressed by melanoma cells in subcutaneous tumors or established lung metastases and on survival (6 mice per group). We also conducted a flow cytometric analysis of systemic CD4+CD25+FOXP3+ T regulatory cells (Tregs) and histological analysis of melanoma tumors. Data were analyzed by Student t test, ANOVA, and log-rank tests. All statistical tests were two-sided.ResultsWe demonstrated non-viral DNA-integrating vectors can be used for stable transgene expression. IFNγ inhibited melanoma cell growth in vitro probably via IFNγ-induced JAK/STAT1 signaling pathway activation. Murine TRAIL induced apoptosis in the human cell lines CAOV-4 and Ej-138, while MCF7 and B16F10 cells appeared to be insensitive to TRAIL. Treatment of melanoma cells with IFNγ did not influence their response to TRAIL. In contrast, results from in vivo studies showed that IFNγ-expressing ADSCs, engrafted into tumor stroma, inhibited tumor growth and angiogenesis, prevented systemic increase of Tregs, increased PD-L1 expression and CD8+ infiltration (but not interleukin-2+ cells), and prolonged the survival of mice (68 days, 95% confidence interval [CI] =52 to 86 days compared to 36 days, 95% CI =29 to 39 days for control, P < .001).ConclusionsFor the first time, we employed DNA integrating vectors for safe and stable modification of MSCs. Our data indicate potential of non-virally modified IFNγ-expressing ADSCs for treatment of melanoma through direct effects of IFNγ. This study may have a significant role in the management of cancer in the future.Electronic supplementary materialThe online version of this article (doi:10.1186/1476-4598-13-255) contains supplementary material, which is available to authorized users.

In this paper, we present a collocation method based on Gaussian Radial Basis Functions (RBFs) for approximating the solution of stochastic fractional differential equations (SFDEs). In this equation the fractional derivative is considered in the Caputo sense. Also we prove the existence and uniqueness of the presented method. Numerical examples confirm the proficiency of the method.