Sofosbuvir Inhibits Hepatitis E Virus Replication In Vitro and Results in an Additive Effect When Combined With Ribavirin.

Infection with hepatitis E virus genotype 3 may result in chronic hepatitis in immunocompromised patients. Reduction of immunosuppression or treatment with ribavirin or pegylated interferon-α can result in viral clearance. However, safer and more effective treatment options are needed. Here, we show that sofosbuvir inhibits the replication of hepatitis E virus genotype 3 both in subgenomic replicon systems as well as a full-length infectious clone. Moreover, the combination of sofosbuvir and ribavirin results in an additive antiviral effect. Sofosbuvir may be considered as an add-on therapy to ribavirin for the treatment of chronic hepatitis E in immunocompromised patients.

An Advocacy for the Use of 3D Stem Cell Culture Systems for the Development of Regenerative Medicine: An Emphasis on Photoreceptor Generation

The availability of stem cells is of great promise to study early developmental stages and to generate adequate cells for cell transfer therapies. Although many researchers using stem cells were successful in dissecting intrinsic and extrinsic mechanisms and in generating specific cell phenotypes, few of the stem cells or the differentiated cells show the capacity to repair a tissue. Advances in cell and stem cell cultivation during the last years made tremendous progress in the generation of bona fide differentiated cells able to integrate into a tissue after transplantation, opening new perspectives for developmental biology studies and for regenerative medicine. In this review, we focus on the main works attempting to create in vitro conditions mimicking the natural environment of CNS structures such as the neural tube and its development in different brain region areas including the optic cup. The use of protocols growing cells in 3D organoids is a key strategy to produce cells resembling endogenous ones. An emphasis on the generation of retina tissue and photoreceptor cells is provided to highlight the promising developments in this field. Other examples are presented and discussed, such as the formation of cortical tissue, the epithelial gut or the kidney organoids. The generation of differentiated tissues and well-defined cell phenotypes from embryonic stem (ES) cells or induced pluripotent cells (iPSCs) opens several new strategies in the field of biology and regenerative medicine. A 3D organ/tissue development in vitro derived from human cells brings a unique tool to study human cell biology and pathophysiology of an organ or a specific cell population. The perspective of tissue repair is discussed as well as the necessity of cell banking to accelerate the progress of this promising field.

Additive effects of rapamycin and aspirin on dendritic cell allostimulatory capacity.

Acting as antigen presenting cells, mature dendritic cells (DCs) initiate both innate and adaptive alloimmune responses. However, immature DCs are weak immunostimulators and mediate tolerogenic effects under certain conditions. Tolerogenic activities of immature DCs can be enhanced by pharmacological agents. Here, we compared pharmacological DC preconditioning with rapamycin and aspirin, applied alone or in combination, on LPS-induced DC maturation and T-cell allostimulatory capacity. Preconditioning with aspirin but not rapamycin tended to reduce the number of mouse bone marrow-derived immature DCs expressing CD40 and major histocompatibility complex class II molecules upon LPS stimulation. Conversely, DC preconditioning with rapamycin, but not aspirin, reduced T-cell alloproliferative responses. A combination of rapamycin and aspirin was more effective than either drug applied alone with respect to inhibition of T-cell alloproliferation. The two agents in combination reduced numbers of CD4(+)IFN-γ(+) Th1 and CD4(+)IL-17(+) Th17 effector cells while maintaining Foxp3(+) regulatory T cells. These results suggest aspirin may moderately enhance rapamycin-mediated inhibition of DC allostimulatory capacity.