Ectopic vascularized bone formation by human umbilical cord-derived mesenchymal stromal cells expressing bone morphogenetic factor-2 and endothelial cells.

Mesenchymal stromal cells (MSCs) isolated from numerous tissues including human fetal tissue are currently used in cell therapy and regenerative medicine. Among fetal tissues, the umbilical cord (UC) is one of the sources for both MSCs and endothelial cells (ECs). To establish ectopic vascularized bone tissue formation, UC-derived MSCs and ECs were isolated. UC-MSCs expressing human BMP-2 (hBMP-2-MSCs) were generated using an adenoviral system to promote bone formation. These cells were then transplanted with Matrigel into the subcutaneous tissue of an immune deficient NSG mouse, and bone tissue was analyzed after several weeks. The osteogenic differentiation ability of MSCs was elevated by transduction of the hBMP-2 expressing adenoviral system, and vascularization of bone tissue was enhanced by human umbilical vein endothelial cells (HUVEC). In this study, our results provide evidence that MSCs and HUVECs from human umbilical cord are suitable cells to investigate bone tissue engineering. The results also suggest that the co-transplantation of hBMP2-MSCs and HUVECs may be a simple and efficient strategy for improving tissue generation and angiogenesis in bone tissue engineering using stem cells.

Degranulation of Mast Cells as a Target for Drug Development.

Mast cells act as key effector cells of inflammatory responses through degranulation. Mast cell degranulation is induced by the activation of cell surface receptors, such as FcεRI, MRGPRX2/B2, and P2RX7. Each receptor, except FcεRI, varies in its expression pattern depending on the tissue, which contributes to their differing involvement in inflammatory responses depending on the site of occurrence. Focusing on the mechanism of allergic inflammatory responses by mast cells, this review will describe newly identified mast cell receptors in terms of their involvement in degranulation induction and patterns of tissue-specific expression. In addition, new drugs targeting mast cell degranulation for the treatment of allergy-related diseases will be introduced.

Combined IgE neutralization and Bifidobacterium longum supplementation reduces the allergic response in models of food allergy.

IgE is central to the development of allergic diseases, and its neutralization alleviates allergic symptoms. However, most of these antibodies are based on IgG1, which is associated with an increased risk of fragment crystallizable-mediated side effects. Moreover, omalizumab, an anti-IgE antibody approved for therapeutic use, has limited benefits for patients with high IgE levels. Here, we assess a fusion protein with extracellular domain of high affinity IgE receptor, FcεRIα, linked to a IgD/IgG4 hybrid Fc domain we term IgETRAP, to reduce the risk of IgG1 Fc-mediated side effects. IgETRAP shows enhanced IgE binding affinity compared to omalizumab. We also see an enhanced therapeutic effect of IgETRAP in food allergy models when combined with Bifidobacterium longum, which results in mast cell number and free IgE levels. The combination of IgETRAP and B. longum may therefore represent a potent treatment for allergic patients with high IgE levels.