Therapeutic potential of human umbilical cord mesenchymal stem cells in the treatment of rheumatoid arthritis

Introduction: Rheumatoid arthritis (RA) is a T-cell-mediated systemic autoimmune disease, characterized by synovium inflammation and articular destruction. Bone marrow mesenchymal stem cells (MSCs) could be effective in the treatment of several autoimmune diseases. However, there has been thus far no report on umbilical cord (UC)-MSCs in the treatment of RA. Here, potential immunosuppressive effects of human UC-MSCs in RA were evaluated. Methods: The effects of UC-MSCs on the responses of fibroblast-like synoviocytes (FLSs) and T cells in RA patients were explored. The possible molecular mechanism mediating this immunosuppressive effect of UC-MSCs was explored by addition of inhibitors to indoleamine 2,3-dioxygenase (IDO), Nitric oxide (NO), prostaglandin E2 (PGE2), transforming growth factor beta 1 (TGF-beta 1) and interleukin 10 (IL-10). The therapeutic effects of systemic infusion of human UC-MSCs on collagen-induced arthritis (CIA) in a mouse model were explored. Results: In vitro, UC-MSCs were capable of inhibiting proliferation of FLSs from RA patients, via IL-10, IDO and TGF-beta 1. Furthermore, the invasive behavior and IL-6 secretion of FLSs were also significantly suppressed. On the other hand, UC-MSCs induced hyporesponsiveness of T cells mediated by PGE2, TGF-beta 1 and NO and UC-MSCs could promote the expansion of CD4(+) Foxp3(+) regulatory T cells from RA patients. More importantly, systemic infusion of human UC-MSCs reduced the severity of CIA in a mouse model. Consistently, there were reduced levels of proinflammatory cytokines and chemokines (TNF-alpha, IL-6 and monocyte chemoattractant protein-1) and increased levels of the anti-inflammatory/regulatory cytokine (IL-10) in sera of UC-MSCs treated mice. Moreover, such treatment shifted Th1/Th2 type responses and induced Tregs in CIA. Conclusions: In conclusion, human UC-MSCs suppressed the various inflammatory effects of FLSs and T cells of RA in vitro, and attenuated the development of CIA in vivo, strongly suggesting that UC-MSCs might be a therapeutic strategy in RA. In addition, the immunosuppressive activitiy of UC-MSCs could be prolonged by the participation of Tregs.http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000287517000020&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=8e1609b174ce4e31116a60747a720701RheumatologySCI(E)PubMed64ARTICLE6R2101

Current views on the role of Notch signaling and the pathogenesis of human leukemia

The Notch signaling pathway is highly conserved from Drosophila to humans and plays an important role in the regulation of cellular proliferation, differentiation and apoptosis

Thinking out of the box - New approaches to controlling GVHD

Graft-versus-host disease (GVHD) remains a major limitation of allogeneic hematopoietic cell transplantation (allo-HCT). Despite major advances in the understanding of GVHD pathogenesis, standard GVHD prophylaxis regimens continue to bebased on the combination of a calcineurin inhibitor with an antimetabolite, while first line treatmentsstill relies on high-dose corticosteroids. Further, no second line treatment has emerged thus far in acute or chronic GVHD patients who failed on corticosteroids. After briefly reviewing current standards of GVHD prevention and treatment, this article will discuss recent approaches that might change GVHD prophylaxis / treatment in the next decades, with a special focus on recently developed immunoregulatory strategies based on infusion of mesenchymal stromal or regulatory T-cells, or on injection of lowdose interleukin-2

First results from the DarkSide-50 dark matter experiment at Laboratori Nazionali del Gran Sasso

© 2015 The Authors. We report the first results of DarkSide-50, a direct search for dark matter operating in the underground Laboratori Nazionali del Gran Sasso (LNGS) and searching for the rare nuclear recoils possibly induced by weakly interacting massive particles (WIMPs). The dark matter detector is a Liquid Argon Time Projection Chamber with a (46.4±0.7)kg active mass, operated inside a 30 t organic liquid scintillator neutron veto, which is in turn installed at the center of a 1 kt water Cherenkov veto for the residual flux of cosmic rays. We report here the null results of a dark matter search for a (1422±67)kgd exposure with an atmospheric argon fill. This is the most sensitive dark matter search performed with an argon target, corresponding to a 90% CL upper limit on the WIMP-nucleon spin-independent cross section of 6.1×10-44cm2 for a WIMP mass of 100Gev/c2

The DarkSide direct dark matter search with liquid argon

International audienceThe DarkSide-50 direct dark matter detector is a liquid argon time projection chamber (TPC) surrounded by a liquid scintillator neutron veto (LSV) and a water Cerenkov muon veto (WCV). Located under 3800 m.w.e. at the Laboratori Nazionali del Gran Sasso, Italy, it is the only direct dark matter experiment currently operating background free. The atmospheric argon target was replaced with argon from underground sources in April, 2015. The level of 39Ar, a β emitter present in atmospheric argon (AAr), has been shown to have been reduced by a factor of (1.4 ± 0.2) x 103. The combined spin-independent WIMP exclusion limit of 2.0 x 10−44 cm2 (mχ = 100 GeV/c2) is currently the best limit on a liquid argon target