Biomechanical Forces Promote Immune Regulatory Function of Bone Marrow Mesenchymal Stromal Cells

Stem Cells. 2017 May;35(5):1259-1272. doi: 10.1002/stem.2587. Epub 2017 Mar 5.


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. Stem Cells 2017;35:1259-1272.

Keywords: Biomechanical force; Immunomodulation; Inflammation; Mesenchymal stromal cells; Shear stress; Traumatic brain injury.

MeSH terms

  • Administration, Intravenous
  • Animals
  • Anti-Inflammatory Agents / metabolism
  • Biomechanical Phenomena
  • Bioreactors
  • Bone Marrow Cells / cytology*
  • Bone Marrow Cells / immunology*
  • Brain Injuries, Traumatic / pathology
  • Brain Injuries, Traumatic / therapy
  • Cyclooxygenase 2 / metabolism
  • Dinoprostone / biosynthesis
  • Humans
  • Immunomodulation
  • Inflammation / pathology
  • Mesenchymal Stem Cell Transplantation
  • Mesenchymal Stem Cells / cytology*
  • Mesenchymal Stem Cells / immunology*
  • Mesenchymal Stem Cells / metabolism
  • Mice, Inbred C57BL
  • NF-kappa B / metabolism
  • Phenotype
  • Rats
  • Rheology
  • Signal Transduction
  • Stress, Mechanical


  • Anti-Inflammatory Agents
  • NF-kappa B
  • Cyclooxygenase 2
  • Dinoprostone