The Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases

Siobahn Evans

 

 

 

 

 

 

Research Project

My current work focuses on the licensing of Mesenchymal Stromal Cells (MSCs) to act as a cellular therapy to suppress inflammation associated with chronic to acute injury, infection autoimmunity, and graft-versus-host disease. MSCs are not spontaneously immunosuppressive and require licensing in order to obtain anti-inflammatory function.  Currently, most licensing efforts involve using cytokines such as TNF-a and IFN-g as well as other compounds such as LPS. My current project includes a novel method of using shear stress to alter the phenotype of MSCs to produce anti-inflammatory factors. Using MSCs activated by shear will reduce production costs associated with cellular therapies and eliminate chances for harmful pharmaceuticals to be transferred to patients.

To gauge the impact of shear stress on MSC immune regulatory function I measure transcript levels of key genes such as TSG-6, IL1RN, COX-2, and HMOX-1 as well as protein level changes and TNF-a ELISAs using LPS activated mouse splenocytes. Potential mechanisms include a signaling cascade propagated by calcium ion influx and NFkB translocation to the nucleus.

Ongoing analysis with models of traumatic brain injury in rats will reveal whether these observed effects translate to in vivo enhancement in function. Planned assays include: vascular permeability of the blood brain barrier (BBB), measurement of spleen size, and behavioral assessment of neurological recovery. Other mechanotransductive experiments in vitro by examining the effects of pressure, microgravity, and stretching on MSC licensing.