Biomechanical Forces Promote Immune Regulatory Function of Bone Marrow Mesenchymal Stromal Cells.
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.
Department of Pediatric Surgery, Children's Regenerative Medicine Program, McGovern Medical School, Houston, Texas, USA.|Center for Stem Cell and Regenerative Medicine, The Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center, Houston, Texas, USA.
Miguel F
MF
Diaz
Department of Pediatric Surgery, Children's Regenerative Medicine Program, McGovern Medical School, Houston, Texas, USA.|Center for Stem Cell and Regenerative Medicine, The Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center, Houston, Texas, USA.
Abishek B
AB
Vaidya
Department of Pediatric Surgery, Children's Regenerative Medicine Program, McGovern Medical School, Houston, Texas, USA.|Center for Stem Cell and Regenerative Medicine, The Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center, Houston, Texas, USA.
Siobahn M
SM
Evans
Department of Pediatric Surgery, Children's Regenerative Medicine Program, McGovern Medical School, Houston, Texas, USA.|Center for Stem Cell and Regenerative Medicine, The Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center, Houston, Texas, USA.
Hyun J
HJ
Lee
Department of Pediatric Surgery, Children's Regenerative Medicine Program, McGovern Medical School, Houston, Texas, USA.
Benjamin M
BM
Aertker
Department of Pediatric Surgery, Children's Regenerative Medicine Program, McGovern Medical School, Houston, Texas, USA.|Center for Stem Cell and Regenerative Medicine, The Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center, Houston, Texas, USA.|Department of BioSciences, Rice University, Houston, Texas, USA.
Alexander J
AJ
Alexander
Department of Pediatric Surgery, Children's Regenerative Medicine Program, McGovern Medical School, Houston, Texas, USA.|Center for Stem Cell and Regenerative Medicine, The Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center, Houston, Texas, USA.|Department of BioSciences, Rice University, Houston, Texas, USA.
Katherine M
KM
Price
Department of Pediatric Surgery, Children's Regenerative Medicine Program, McGovern Medical School, Houston, Texas, USA.|Center for Stem Cell and Regenerative Medicine, The Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center, Houston, Texas, USA.|Department of BioSciences, Rice University, Houston, Texas, USA.
Joyce A
JA
Ozuna
Department of Pediatric Surgery, Children's Regenerative Medicine Program, McGovern Medical School, Houston, Texas, USA.
George P
GP
Liao
Department of Pediatric Surgery, Children's Regenerative Medicine Program, McGovern Medical School, Houston, Texas, USA.
Kevin R
KR
Aroom
Department of Pediatric Surgery, Children's Regenerative Medicine Program, McGovern Medical School, Houston, Texas, USA.
Hasen
H
Xue
Department of Pediatric Surgery, Children's Regenerative Medicine Program, McGovern Medical School, Houston, Texas, USA.|Center for Stem Cell and Regenerative Medicine, The Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center, Houston, Texas, USA.
Liang
L
Gu
Department of Pediatric Surgery, Children's Regenerative Medicine Program, McGovern Medical School, Houston, Texas, USA.|Center for Stem Cell and Regenerative Medicine, The Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center, Houston, Texas, USA.|School of Medicine, Faculty of Medicine, Tokushima University, Tokushima, Japan.
Rui
R
Omichi
Department of Pediatric Surgery, Children's Regenerative Medicine Program, McGovern Medical School, Houston, Texas, USA.
Supinder
S
Bedi
Department of Pediatric Surgery, Children's Regenerative Medicine Program, McGovern Medical School, Houston, Texas, USA.
Scott D
0000-0001-8032-3755
SD
Olson
Department of Pediatric Surgery, Children's Regenerative Medicine Program, McGovern Medical School, Houston, Texas, USA.|Center for Stem Cell and Regenerative Medicine, The Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center, Houston, Texas, USA.
Charles S
CS
Cox
Department of Pediatric Surgery, Children's Regenerative Medicine Program, McGovern Medical School, Houston, Texas, USA.|Center for Stem Cell and Regenerative Medicine, The Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center, Houston, Texas, USA.
Pamela L
0000-0002-4530-015X
PL
Wenzel
D061605:Administration, Intravenous; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000378:metabolism; D001696:Biomechanical Phenomena; D019149:Bioreactors; D001854:Bone Marrow Cells / Q000166:cytology* / Q000276:immunology*; D000070642:Brain Injuries, Traumatic / Q000473:pathology / Q000628:therapy; D051546:Cyclooxygenase 2 / Q000378:metabolism; D015232:Dinoprostone / Q000096:biosynthesis; D006801:Humans; D056747:Immunomodulation; D007249:Inflammation / Q000473:pathology; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D010641:Phenotype; D051381:Rats; D012212:Rheology; D015398:Signal Transduction; D013314:Stress, Mechanical
D000893:Anti-Inflammatory Agents; D016328:NF-kappa B; D051546:Cyclooxygenase 2; D015232:Dinoprostone
Biomechanical force; Immunomodulation; Inflammation; Mesenchymal stromal cells; Shear stress; Traumatic brain injury