TGFβ1 priming enhances CXCR3-mediated mesenchymal stromal cell engraftment to the liver and enhances anti-inflammatory efficacy

Abhilok Garg; Sheeba Khan; N Luu; Davies J Nicholas; Victoria Day; Andrew L King; Janine Fear; Patricia F Lalor; Philip N Newsome

doi:10.1111/jcmm.17698

TGFβ₁ priming enhances CXCR3-mediated mesenchymal stromal cell engraftment to the liver and enhances anti-inflammatory efficacy

Abhilok Garg, Sheeba Khan, N Luu, Davies J Nicholas, Victoria Day, Andrew L King, Janine Fear, Patricia F Lalor, Philip N Newsome^*

^*Corresponding author for this work

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

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Abstract

The immunomodulatory characteristics of mesenchymal stromal cells (MSC) confers them with potential therapeutic value in the treatment of inflammatory/immune-mediated conditions. Previous studies have reported only modest beneficial effects in murine models of liver injury. In our study we explored the role of MSC priming to enhance their effectiveness. Herein we demonstrate that stimulation of human MSC with cytokine TGβ₁ enhances their homing and engraftment to human and murine hepatic sinusoidal endothelium in vivo and in vitro, which was mediated by increased expression of CXCR3. Alongside improved hepatic homing there was also greater reduction in liver inflammation and necrosis, with no adverse effects, in the CCL₄ murine model of liver injury treated with primed MSC. Priming of MSCs with TGFβ₁is a novel strategy to improve the anti-inflammatory efficacy of MSCs.

Original language	English
Pages (from-to)	864-878
Number of pages	15
Journal	Journal of Cellular and Molecular Medicine
Volume	27
Issue number	6
Early online date	23 Feb 2023
DOIs	https://doi.org/10.1111/jcmm.17698
Publication status	Published - Mar 2023

Bibliographical note

Keywords

Humans
Animals
Mice
Cytokines/metabolism
Liver/metabolism
Anti-Inflammatory Agents/metabolism
Mesenchymal Stem Cells/metabolism
Mesenchymal Stem Cell Transplantation
Receptors, CXCR3/metabolism
immunomodulation
macrophages
homing

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Cite this

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title = "TGFβ1 priming enhances CXCR3-mediated mesenchymal stromal cell engraftment to the liver and enhances anti-inflammatory efficacy",

abstract = "The immunomodulatory characteristics of mesenchymal stromal cells (MSC) confers them with potential therapeutic value in the treatment of inflammatory/immune-mediated conditions. Previous studies have reported only modest beneficial effects in murine models of liver injury. In our study we explored the role of MSC priming to enhance their effectiveness. Herein we demonstrate that stimulation of human MSC with cytokine TGβ1 enhances their homing and engraftment to human and murine hepatic sinusoidal endothelium in vivo and in vitro, which was mediated by increased expression of CXCR3. Alongside improved hepatic homing there was also greater reduction in liver inflammation and necrosis, with no adverse effects, in the CCL4 murine model of liver injury treated with primed MSC. Priming of MSCs with TGFβ1 is a novel strategy to improve the anti-inflammatory efficacy of MSCs.",

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author = "Abhilok Garg and Sheeba Khan and N Luu and Nicholas, {Davies J} and Victoria Day and King, {Andrew L} and Janine Fear and Lalor, {Patricia F} and Newsome, {Philip N}",

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T1 - TGFβ1 priming enhances CXCR3-mediated mesenchymal stromal cell engraftment to the liver and enhances anti-inflammatory efficacy

AU - Garg, Abhilok

AU - Khan, Sheeba

AU - Luu, N

AU - Nicholas, Davies J

AU - Day, Victoria

AU - King, Andrew L

AU - Fear, Janine

AU - Lalor, Patricia F

AU - Newsome, Philip N

PY - 2023/3

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N2 - The immunomodulatory characteristics of mesenchymal stromal cells (MSC) confers them with potential therapeutic value in the treatment of inflammatory/immune-mediated conditions. Previous studies have reported only modest beneficial effects in murine models of liver injury. In our study we explored the role of MSC priming to enhance their effectiveness. Herein we demonstrate that stimulation of human MSC with cytokine TGβ1 enhances their homing and engraftment to human and murine hepatic sinusoidal endothelium in vivo and in vitro, which was mediated by increased expression of CXCR3. Alongside improved hepatic homing there was also greater reduction in liver inflammation and necrosis, with no adverse effects, in the CCL4 murine model of liver injury treated with primed MSC. Priming of MSCs with TGFβ1 is a novel strategy to improve the anti-inflammatory efficacy of MSCs.

AB - The immunomodulatory characteristics of mesenchymal stromal cells (MSC) confers them with potential therapeutic value in the treatment of inflammatory/immune-mediated conditions. Previous studies have reported only modest beneficial effects in murine models of liver injury. In our study we explored the role of MSC priming to enhance their effectiveness. Herein we demonstrate that stimulation of human MSC with cytokine TGβ1 enhances their homing and engraftment to human and murine hepatic sinusoidal endothelium in vivo and in vitro, which was mediated by increased expression of CXCR3. Alongside improved hepatic homing there was also greater reduction in liver inflammation and necrosis, with no adverse effects, in the CCL4 murine model of liver injury treated with primed MSC. Priming of MSCs with TGFβ1 is a novel strategy to improve the anti-inflammatory efficacy of MSCs.

KW - Humans

KW - Animals

KW - Mice

KW - Cytokines/metabolism

KW - Liver/metabolism

KW - Anti-Inflammatory Agents/metabolism

KW - Mesenchymal Stem Cells/metabolism

KW - Mesenchymal Stem Cell Transplantation

KW - Receptors, CXCR3/metabolism

KW - immunomodulation

KW - macrophages

KW - homing

U2 - 10.1111/jcmm.17698

DO - 10.1111/jcmm.17698

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SN - 1582-1838

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JO - Journal of Cellular and Molecular Medicine

JF - Journal of Cellular and Molecular Medicine

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