Glypican 4 down-regulation in pluripotent stem cells as a potential strategy to improve differentiation and to impair tumorigenicity of cell transplants

Recent advances in stem cell technologies have opened new avenues for the treatment of a number of diseases still lacking effective therapeutic options.Cell transplantation has emerged as among the most promising clinical intervention for disorders such as injuries,diabetes,liver diseases, neurodegeneration and heart failure （Lee et al., 2013; Forbes and Rosenthal, 2014; Tabar and Studer, 2014）.

Cyclosporin A impairs dendritic cell migration by regulating chemokine receptor expression and inhibiting cyclooxygenase-2 expression

Migration of dendritic cells (DCs) into tissues and secondary lymphoid organs plays a crucial role in the initiation of innate and adaptive immunity. In this article, we show that cyclosporin A (CsA) impairs the migration of DCs both in vitro and in vivo. Exposure of DCs to clinical concentrations of CsA neither induces apoptosis nor alters development but does impair cytokine secretion, chemokine receptor expression, and migration. In vitro, CsA impairs the migration of mouse bone marrow-derived DCs toward macrophage inflammatory protein-3beta (MIP-3beta) and induces them to retain responsiveness to MIP-1alpha after lipopolysaccharide (LPS)-stimulated DC maturation, while in vivo administration of CsA inhibits the migration of DCs out of skin and into the secondary lymphoid organs. CsA impairs chemokine receptor and cyclooxygenase-2 (COX-2) expression normally triggered in LPS-stimulated DCs; administration of exogenous prostaglandin E2 (PGE2) reverses the effects of CsA on chemokine receptor expression and DC migration. Inhibition of nuclear factor-kappaB (NF-κB) and mitogen-activated protein kinase (MAPK) pathway signaling by CsA may be responsible for the CsA-mediated effects on the regulation of chemokine receptor and cyclooxygenase-2 (COX-2) expression. Impairment of DC migration due to inhibition of PGE2 production and regulation of chemokine receptor expression may contribute, in part, to CsA-mediated immunosuppression.

The promise of stem cells in the therapy of Alzheimer’s disease

Alzheimer’s disease(AD),a common neurodegenerative disorder associated with gradually to dramatic neuronal death,synaptic loss and dementia,is considered to be one of the most obscure and intractable brain disorders in medicine.Currently,there is no therapy clinically available to induce marked symptomatic relief in AD patients.In recent years,the proof-of-concept studies using stem cell-based approaches in transgenic AD animal models provide new hope to develop stem cell-based therapies for the effective treatment of AD.The degeneration of basal forebrain cholinergic neurons(BFCNs)and the resultant cholinergic abnormalities in the brain contribute substantially to the cognitive decline of AD patients.The approches using stem cell-derived BFCNs as donor cells need to be developed,and to provide proof of principle that this subtype-specific neurons can induce functional recovery of AD animal models.With the continuous scientific advances in both academic and industrial fields,the potentials of stem cells in cellular neuroprotection and cell replacement in vivo have been elucidated,and stem cell-based therapy for repairing degenerative brains of AD is promising.