Open AccessBiomechanical Forces Promote Immune Regulatory Function of Bone Marrow Mesenchymal Stromal Cells
Author(s) -
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.
Publication year - 2017
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.2587
Subject(s) - mesenchymal stem cell , biology , stromal cell , immune system , chemokine , bone marrow , inflammation , paracrine signalling , tumor necrosis factor alpha , microbiology and biotechnology , clinical uses of mesenchymal stem cells , stem cell , immunology , cancer research , adult stem cell , endothelial stem cell , in vitro , receptor , biochemistry
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 E 2 (PGE 2 ) 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. S tem C ells 2017;35:1259–1272