Mesenchymal stem cells induce functionally active T-regulatory lymphocytes in a paracrine fashion and ameliorate experimental autoimmune uveitis.

Purpose: Mesenchymal stem/progenitor cells (MSCs) have regenerative and immunomodulatory properties, exerted by cell-cell contact and in a paracrine fashion. Part of their immunosuppressive activity has been ascribed to their ability to promote the induction of CD4+CD25+FoxP3+ T lymphocytes with regulatory functions (Treg). Here the authors studied the effect of MSCs on the induction of Treg and on the development of autoimmunity, and they examined the possibility that MSC-mediated Treg induction could be attributed to the secretion of soluble factors.

Regulation of human mesenchymal stem cell functions by an autocrine loop involving NAD+ release and P2Y11-mediated signaling.

In several cell types, a regulated efflux of NAD(+) across Connexin 43 hemichannels (Cx43 HC) can occur, and extracellular NAD(+) (NAD(+)(e)) affects cell-specific functions. We studied the capability of bone marrow-derived human mesenchymal stem cells (MSC) to release intracellular NAD(+) through Cx43 HC. NAD(+) efflux, quantified by a sensitive enzymatic cycling assay, was significantly upregulated by low extracellular Ca(2+) (5-6-fold), by shear stress (13-fold), and by inflammatory conditions (3.

A composite material model for improved bone formation.

The combination of synthetic polymers and calcium phosphates represent an improvement in the development of scaffolds for bone-tissue regeneration. Ideally, these composites provide both mechanically and architecturally enhanced performances; however, they often lack properties such as osteoconductivity and cell bioactivation. In this study we attempted to generate a composite bone substitute maximizing the available osteoconductive surface for cell adhesion and activity.

Short-time survival and engraftment of bone marrow stromal cells in an ectopic model of bone regeneration.

In tissue-engineered applications bone marrow stromal cells (BMSCs) are combined with scaffolds to target bone regeneration; animal models have been devised and the cells' long-term engraftment has been widely studied. However, in regenerated bone, the cell number is severely reduced with respect to the initially seeded BMSCs. This reflects the natural low cellularity of bone but underlines the selectivity of the differentiation processes.

Hydroxyapatite-coated polycaprolacton wide mesh as a model of open structure for bone regeneration.

In principle, three-dimensional (3D) osteoconductive grafts with a proper chemical composition, high total porosity, and fully interconnected pores are suitable carriers to provide a proper substrate for in vivo neobone tissue ingrowth. However, most porous materials carry some intrinsic limits because of their internal structure (i.e.

The Wnt/beta-catenin-->Pitx2 pathway controls the turnover of Pitx2 and other unstable mRNAs.

The Wnt/beta-catenin pathway rapidly induces the transcription of the cell-type-restricted transcription factor Pitx2 that is required for effective cell-specific proliferation activating growth-regulating genes. Here we report that Pitx2 mRNA displays a rapid turnover rate and that activation of the Wnt/beta-catenin pathway stabilizes Pitx2 mRNA as well as other unstable mRNAs, including c-Jun, Cyclin D1, and Cyclin D2, encoded by critical transcriptional target genes of the same pathway. Our data indicate that Pitx2 mRNA stabilization is due to a reduced interaction of Pitx2 3'UTR with the destabilizing AU-rich element (ARE) binding proteins (BPs) KSRP and TTP as well as to an increased interaction with a stabilizing ARE-BP, HuR.