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

Miguel F. Diaz; Abishek B. Vaidya; Siobahn M. Evans; Hyun J. Lee; Benjamin M. Aertker; Alexander J. Alexander; Katherine M. Price; Joyce A. Ozuna; George P. Liao; Kevin R. Aroom; Hasen Xue; Liang Gu; Rui Omichi; Supinder Bedi; Scott D. Olson; Charles S. Cox; Pamela L. Wenzel

doi:10.1002/stem.2587

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

Miguel F. Diaz, Abishek B. Vaidya, Siobahn M. Evans, Hyun J. Lee, Benjamin M. Aertker, Alexander J. Alexander, Katherine M. Price, Joyce A. Ozuna, George P. Liao, Kevin R. Aroom, Hasen Xue, Liang Gu, Rui Omichi, Supinder Bedi, Scott D. Olson, Charles S. Cox, Pamela L. Wenzel

Research output: Contribution to journal › Article › peer-review

46 Scopus citations

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. Stem Cells 2017;35:1259–1272.

Original language	English
Pages (from-to)	1259-1272
Number of pages	14
Journal	Stem Cells
Volume	35
Issue number	5
DOIs	https://doi.org/10.1002/stem.2587
State	Published - May 2017
Externally published	Yes

Keywords

Biomechanical force
Immunomodulation
Inflammation
Mesenchymal stromal cells
Shear stress
Traumatic brain injury

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10.1002/stem.2587

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Diaz, M. F., Vaidya, A. B., Evans, S. M., Lee, H. J., Aertker, B. M., Alexander, A. J., Price, K. M., Ozuna, J. A., Liao, G. P., Aroom, K. R., Xue, H., Gu, L., Omichi, R., Bedi, S., Olson, S. D., Cox, C. S., & Wenzel, P. L. (2017). Biomechanical Forces Promote Immune Regulatory Function of Bone Marrow Mesenchymal Stromal Cells. Stem Cells, 35(5), 1259-1272. https://doi.org/10.1002/stem.2587

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title = "Biomechanical Forces Promote Immune Regulatory Function of Bone Marrow Mesenchymal Stromal Cells",

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. Stem Cells 2017;35:1259–1272.",

keywords = "Biomechanical force, Immunomodulation, Inflammation, Mesenchymal stromal cells, Shear stress, Traumatic brain injury",

author = "Diaz, {Miguel F.} and Vaidya, {Abishek B.} and Evans, {Siobahn M.} and Lee, {Hyun J.} and Aertker, {Benjamin M.} and Alexander, {Alexander J.} and Price, {Katherine M.} and Ozuna, {Joyce A.} and Liao, {George P.} and Aroom, {Kevin R.} and Hasen Xue and Liang Gu and Rui Omichi and Supinder Bedi and Olson, {Scott D.} and Cox, {Charles S.} and Wenzel, {Pamela L.}",

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year = "2017",

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doi = "10.1002/stem.2587",

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AU - Aertker, Benjamin M.

AU - Alexander, Alexander J.

AU - Price, Katherine M.

AU - Ozuna, Joyce A.

AU - Liao, George P.

AU - Aroom, Kevin R.

AU - Xue, Hasen

AU - Gu, Liang

AU - Omichi, Rui

AU - Bedi, Supinder

AU - Olson, Scott D.

AU - Cox, Charles S.

AU - Wenzel, Pamela L.

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N2 - 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.

AB - 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.

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KW - Immunomodulation

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

Abstract

Keywords

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