Biomechanical Forces Promote Immune Regulatory Function of Bone Marrow Mesenchymal Stromal Cells. (5th March 2017)

• Record Type: Journal Article
• Authors: Diaz, Miguel F.; Vaidya, Abishek B.; Evans, Siobahn M.; Lee, Hyun J.; Aertker, Benjamin M.; Alexander, Alexander J.; Price, Katherine M.; Ozuna, Joyce A.; Liao, George P.; Aroom, Kevin R.; Xue, Hasen; Gu, Liang; Omichi, Rui; Bedi, Supinder; Olson, Scott D.; Cox, Charles S.; Wenzel, Pamela L.
• Is Part Of: Stem cells. Volume 35:Number 5(2017:May)
• Page Start: 1259
• Page End: 1272
• Publication Date: 2017-03-05
• Subjects: Biomechanical force -- Mesenchymal stromal cells -- Immunomodulation -- Inflammation -- Shear stress -- Traumatic brain injury; Cloning -- Periodicals; Clone cells -- Periodicals; Stem cells -- Periodicals; Cell Differentiation -- Periodicals; Cell Division -- Periodicals; Clone Cells -- Periodicals; Hematopoietic Stem Cells -- Periodicals; Stem Cells -- Periodicals; 571.84
• DOI: 10.1002/stem.2587
• Languages: English
• ISSNs: 1066-5099

Abstract

Abstract : Mesenchymal stromal cells (MSCs) are believed to mobilize from the bone marrow in response to inflammation and injury, yet the effects of egress into the vasculature on MSC function are largely unknown. Here we show that wall shear stress (WSS) typical of fluid frictional forces present on the vascular lumen stimulates antioxidant and anti-inflammatory mediators, as well as chemokines capable of immune cell recruitment. WSS specifically promotes signaling through NFκB-COX2-prostaglandin E2 (PGE2 ) to suppress tumor necrosis factor-α (TNF-α) production by activated immune cells. Ex vivo conditioning of MSCs by WSS improved therapeutic efficacy in a rat model of traumatic brain injury, as evidenced by decreased apoptotic and M1-type activated microglia in the hippocampus. These results demonstrate that force provides critical cues to MSCs residing at the vascular interface which influence immunomodulatory and paracrine activity, and suggest the potential therapeutic use of force for MSC functional enhancement.