Cytokine treatment optimises the immunotherapeutic effects of umbilical cord-derived MSC for treatment of inflammatory liver disease

Background: Mesenchymal stromal cells (MSC) possess immunomodulatory properties and low immunogenicity, both crucial properties for their development into an effective cellular immunotherapy. They have shown benefit in clinical trials targeting liver diseases; however the efficacy of MSC therapy will benefit from improvement of the immunomodulatory and immunogenic properties of MSC. Methods: MSC derived from human umbilical cords (ucMSC) were treated for 3 days in vitro with various inflammatory factors, interleukins, vitamins and serum deprivation. Their immunogenicity and immunomodulatory capacity were examined by gene-expression analysis, surface-marker expressions, IDO activity, PGE2 secretion and inhibition of T cell proliferation and IFNγ production. Furthermore, their activation of NK cell cytotoxicity was investigated via CD107a expre

Validation of parameter estimation methods for determining optical properties of atherosclerotic tissues in intravascular OCT

In this paper we present a new process for assessing optical properties of tissues from 3D pullbacks, the standard clinical acquisition method for iOCT data. Our method analyzes a volume of interest (VOI) consisting of about 100 A-lines spread across the angle of rotation (\u3b8) and along the artery, z. The new 3D method uses catheter correction, baseline removal, speckle noise reduction, alignment of A-line sequences, and robust estimation. We compare results to those from a more standard, gold standard stationary acquisition where many image frames are averaged to reduce noise. To do these studies in a controlled fashion, we use a realistic optical artery phantom containing of multiple tissue types. Precision and accuracy for 3D pullback analysis are reported. Our results indicate that when implementing the process on a stationary acquisition dataset, the uncertainty improves at each stage while the uncertainty is reduced. When comparing stationary acquisition dataset to pullback dataset, the values were as follows: calcium: 3.8\ub11.09mm -1 in stationary and 3.9\ub11.2 mm-1 in a pullback; lipid: 11.025\ub10.417 mm-1 in stationary and 11.27\ub10.25 mm-1 in pullback; fibrous: 6.08\ub11.337 mm-1 in stationary and 5.58\ub12.0 mm-1. These results indicates that the process presented in this paper introduce minimal bias and only a small change in uncertainty when comparing a stationary and pullback dataset, thus paves the way to a highly accurate clinical plaque type discrimination, enabling automatic classification.Peer reviewed: YesNRC publication: Ye

Inactivated Mesenchymal Stem Cells Maintain Immunomodulatory Capacity

Mesenchymal stem cells (MSC) are studied as a cell therapeutic agent for treatment of various immune diseases. However, therapy with living culture-expanded cells comes with safety concerns. Furthermore, development of effective MSC immunotherapy is hampered by lack of knowledge of the mechanisms of action and the therapeutic components of MSC. Such knowledge allows better identification of diseases that are responsive to MSC treatment, optimization of the MSC product, and development of therapy based on functional components of MSC. To close in on the components that carry the therapeutic immunomodulatory activity of MSC, we generated MSC that were unable to respond to inflammatory signals or secrete immunomodulatory factors, but preserved their cellular integrity [heat-inactivated MSC (HI-MSC)]. Secretome-deficient HI-MSC and control MSC showed the same biodistribution and persistence after infusion in mice with ischemic kidney injury. Both control and HI-MSC induced mild inflammatory responses in healthy mice and dramatic increases in interleukin-10, and reductions in interferon gamma levels in sepsis mice. In vitro experiments showed that opposite to control MSC, HI-MSC lacked the capability to suppress T-cell proliferation or induce regulatory B-cell formation. However, both HI-MSC and control MSC modulated monocyte function in response to lipopolysaccharides. The results of this study demonstrate that, in particular disease models, the immunomodulatory effect of MSC does not depend on their secretome or active cross-talk with immune cells, but on recognition of MSC by monocytic cells. These findings provide a new view on MSC-induced immunomodulation and help identify key components of the therapeutic effects of MSC