Inflammatory cytokine induced regulation of superoxide dismutase 3 expression by human mesenchymal stem cells
ABSTRACT Increasing evidence suggests that bone marrow derived-mesenchymal stem cells (MSCs) have neuroprotective properties and a major mechanism of action is through their capacity to secrete a diverse range of potentially neurotrophic or anti-oxidant factors. The recent discovery that MSCs secrete superoxide dismutase 3 (SOD3) may help explain studies in which MSCs have a direct anti-oxidant activity that is conducive to neuroprotection in both in vivo and in vitro. SOD3 attenuates tissue damage and reduces inflammation and may confer neuroprotective effects against nitric oxide-mediated stress to cerebellar neurons; but, its role in relation to central nervous system inflammation and neurodegeneration has not been extensively investigated. Here we have performed a series of experiments showing that SOD3 secretion by human bone marrow-derived MSCs is regulated synergistically by the inflammatory cytokines TNF-alpha and IFN-gamma, rather than through direct exposure to reactive oxygen species. Furthermore, we have shown SOD3 secretion by MSCs is increased by activated microglial cells. We have also shown that MSCs and recombinant SOD are able to increase both neuronal and axonal survival in vitro against nitric oxide or microglial induced damage, with an increased MSC-induced neuroprotective effect evident in the presence of inflammatory cytokines TNF-alpha and IFN-gamma. We have shown MSCs are able to convey these neuroprotective effects through secretion of soluble factors alone and furthermore demonstrated that SOD3 secretion by MSCs is, at least, partially responsible for this phenomenon. SOD3 secretion by MSCs maybe of relevance to treatment strategies for inflammatory disease of the central nervous system.
- SourceAvailable from: PubMed Central
[Show abstract] [Hide abstract]
- "In line with Oh et al. , we could also demonstrate that MSCs request IFN-γ for the production of NO, which is known for its antiapoptotic  and antiviral properties . Furthermore, Kemp et al.  demonstrated that the secretion of the antioxidative enzyme superoxide dismutase 3 by MSCs is regulated synergistically by TNF-α and IFN-γ, rather than through direct exposure to reactive oxygen species. "
ABSTRACT: Under conventional heart failure therapy, inflammatory cardiomyopathy usually has a progressive course, merging for alternative interventional strategies. There is accumulating support for the application of cellular transplantation as a strategy to improve myocardial function. Mesenchymal stem cells (MSCs) have the advantage over other stem cells that they possess immunomodulatory features, making them attractive candidates for the treatment of inflammatory cardiomyopathy. Studies in experimental models of inflammatory cardiomyopathy have consistently demonstrated the potential of MSCs to reduce cardiac injury and to improve cardiac function. This paper gives an overview about how inflammation triggers the functionality of MSCs and how it induces cardiac homing. Finally, the potential of intravenous application of MSCs by inflammatory cardiomyopathy is discussed.03/2011; 2011:757154. DOI:10.4061/2011/757154
- [Show abstract] [Hide abstract]
ABSTRACT: The Manufacturing Message Specification (MMS) is an OSI application layer standard designed to support messaging communications to and from programmable devices in a computer integrated manufacturing (CIM) environment. This paper describes how the ISO Development Environment (ISODE) can be employed to implement MMS. ISODE is a non-proprietary implementation of the upper layers of the OSI protocol suite. The experience should be useful to those contemplating using ISODE to implement OSI application entities and application programsTENCON '93. Proceedings. Computer, Communication, Control and Power Engineering.1993 IEEE Region 10 Conference on; 11/1993
Conference Paper: Development update of a 10 MW, 91 GHz gyroklystron[Show abstract] [Hide abstract]
ABSTRACT: Calabazas Creek Research, Inc. (CCR) is funded by the U.S. Department of Energy to develop a high efficiency gyroklystron amplifier for W-Band linear collider applications. This research supports an international effort to design the next generation of linear electron-positron colliders with anticipated center of mass energies of 0.5 TeV and beyond. In particular, this program supports development of a W-Band accelerator now underway at the Stanford Linear Accelerator Center. CCR is developing a 91.392 GHz gyroklystron to produce 10 MW of RF power with efficiency greater than 40% and a gain of 55 dB. Achievement of 10 MW of peak power would advance the state of the art for W-Band amplifiers by two orders of magnitude and potentially lead to other applications, including land- and ship-based radar, medical accelerators, and materials processing.Vacuum Electronics Conference, 2002. IVEC 2002. Third IEEE International; 02/2002