Mesenchymal stromal cells reset the scatter factor system and cytokine network in experimental kidney transplantation

Marilena Gregorini, Francesca Bosio, Chiara Rocca, Valeria Corradetti, Teresa Valsania, Eleonora Francesca Pattonieri, Pasquale Esposito, Giulia Bedino, Chiara Collesi, Carmelo Libetta, Francesco Frassoni, Antonio Dal Canton, Teresa Rampino

Research output: Contribution to journalArticle

Abstract

Background: In former studies we showed in a rat model of renal transplantation that Mesenchymal Stromal Cells (MSC) prevent acute rejection in an independent way of their endowing in the graft. In this study we investigated whether MSC operate by resetting cytokine network and Scatter Factor systems, i.e. Hepatocyte Growth Factor (HGF), Macrophage Stimulating Protein (MSP) and their receptors Met and RON, respectively. Methods: MSC were injected into the renal artery soon after reperfusion. Controls were grafted untreated and normal rats. Rats were sacrificed 7 days after grafting. Serum and renal tissue levels of IFN-γ, IL-1, IL-2, IL-4, IL-6, IL-10, MSP/RON, HGF/Met systems, Treg lymphocytes were investigated. Results: In grafted untreated rats IFN-γ increased in serum and renal tissue and IL-6 rose in serum. MSC prevented both the phenomena, increased IL-10 serum levels and Treg number in the graft. Furthermore MSC increased serum and tissue HGF levels, Met tubular expression and prevented the suppression of tubular MSP/RON expression. Conclusions: Our results demonstrate that MSC modify cytokine network to a tolerogenic setting, they suppress Th1 cells, inactivate monocytes/macrophage, recruit Tregs. In addition, MSC sustain the expression of the Scatter Factor systems expression, i.e. systems that are committed to defend survival and stimulate regeneration of tubular cells.

Original languageEnglish
Article number44
JournalBMC Immunology
Volume15
Issue number1
DOIs
Publication statusPublished - Oct 3 2014

Fingerprint

Hepatocyte Growth Factor
Mesenchymal Stromal Cells
Kidney Transplantation
Cytokines
Serum
Interleukin-10
Interleukin-6
Transplants
Kidney
Th1 Cells
Renal Artery
Interleukin-1
Interleukin-4
Reperfusion
Interleukin-2
Regeneration
Monocytes
Macrophages
Lymphocytes
rice bran saccharide

Keywords

  • Acute kidney rejection
  • Experimental model
  • Hepatocyte growth factor
  • Macrophage stimulating protein
  • Mesenchymal stromal cells
  • Scatter factors

ASJC Scopus subject areas

  • Immunology
  • Medicine(all)

Cite this

Mesenchymal stromal cells reset the scatter factor system and cytokine network in experimental kidney transplantation. / Gregorini, Marilena; Bosio, Francesca; Rocca, Chiara; Corradetti, Valeria; Valsania, Teresa; Pattonieri, Eleonora Francesca; Esposito, Pasquale; Bedino, Giulia; Collesi, Chiara; Libetta, Carmelo; Frassoni, Francesco; Dal Canton, Antonio; Rampino, Teresa.

In: BMC Immunology, Vol. 15, No. 1, 44, 03.10.2014.

Research output: Contribution to journalArticle

Gregorini, Marilena ; Bosio, Francesca ; Rocca, Chiara ; Corradetti, Valeria ; Valsania, Teresa ; Pattonieri, Eleonora Francesca ; Esposito, Pasquale ; Bedino, Giulia ; Collesi, Chiara ; Libetta, Carmelo ; Frassoni, Francesco ; Dal Canton, Antonio ; Rampino, Teresa. / Mesenchymal stromal cells reset the scatter factor system and cytokine network in experimental kidney transplantation. In: BMC Immunology. 2014 ; Vol. 15, No. 1.
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abstract = "Background: In former studies we showed in a rat model of renal transplantation that Mesenchymal Stromal Cells (MSC) prevent acute rejection in an independent way of their endowing in the graft. In this study we investigated whether MSC operate by resetting cytokine network and Scatter Factor systems, i.e. Hepatocyte Growth Factor (HGF), Macrophage Stimulating Protein (MSP) and their receptors Met and RON, respectively. Methods: MSC were injected into the renal artery soon after reperfusion. Controls were grafted untreated and normal rats. Rats were sacrificed 7 days after grafting. Serum and renal tissue levels of IFN-γ, IL-1, IL-2, IL-4, IL-6, IL-10, MSP/RON, HGF/Met systems, Treg lymphocytes were investigated. Results: In grafted untreated rats IFN-γ increased in serum and renal tissue and IL-6 rose in serum. MSC prevented both the phenomena, increased IL-10 serum levels and Treg number in the graft. Furthermore MSC increased serum and tissue HGF levels, Met tubular expression and prevented the suppression of tubular MSP/RON expression. Conclusions: Our results demonstrate that MSC modify cytokine network to a tolerogenic setting, they suppress Th1 cells, inactivate monocytes/macrophage, recruit Tregs. In addition, MSC sustain the expression of the Scatter Factor systems expression, i.e. systems that are committed to defend survival and stimulate regeneration of tubular cells.",
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AU - Gregorini, Marilena

AU - Bosio, Francesca

AU - Rocca, Chiara

AU - Corradetti, Valeria

AU - Valsania, Teresa

AU - Pattonieri, Eleonora Francesca

AU - Esposito, Pasquale

AU - Bedino, Giulia

AU - Collesi, Chiara

AU - Libetta, Carmelo

AU - Frassoni, Francesco

AU - Dal Canton, Antonio

AU - Rampino, Teresa

PY - 2014/10/3

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N2 - Background: In former studies we showed in a rat model of renal transplantation that Mesenchymal Stromal Cells (MSC) prevent acute rejection in an independent way of their endowing in the graft. In this study we investigated whether MSC operate by resetting cytokine network and Scatter Factor systems, i.e. Hepatocyte Growth Factor (HGF), Macrophage Stimulating Protein (MSP) and their receptors Met and RON, respectively. Methods: MSC were injected into the renal artery soon after reperfusion. Controls were grafted untreated and normal rats. Rats were sacrificed 7 days after grafting. Serum and renal tissue levels of IFN-γ, IL-1, IL-2, IL-4, IL-6, IL-10, MSP/RON, HGF/Met systems, Treg lymphocytes were investigated. Results: In grafted untreated rats IFN-γ increased in serum and renal tissue and IL-6 rose in serum. MSC prevented both the phenomena, increased IL-10 serum levels and Treg number in the graft. Furthermore MSC increased serum and tissue HGF levels, Met tubular expression and prevented the suppression of tubular MSP/RON expression. Conclusions: Our results demonstrate that MSC modify cytokine network to a tolerogenic setting, they suppress Th1 cells, inactivate monocytes/macrophage, recruit Tregs. In addition, MSC sustain the expression of the Scatter Factor systems expression, i.e. systems that are committed to defend survival and stimulate regeneration of tubular cells.

AB - Background: In former studies we showed in a rat model of renal transplantation that Mesenchymal Stromal Cells (MSC) prevent acute rejection in an independent way of their endowing in the graft. In this study we investigated whether MSC operate by resetting cytokine network and Scatter Factor systems, i.e. Hepatocyte Growth Factor (HGF), Macrophage Stimulating Protein (MSP) and their receptors Met and RON, respectively. Methods: MSC were injected into the renal artery soon after reperfusion. Controls were grafted untreated and normal rats. Rats were sacrificed 7 days after grafting. Serum and renal tissue levels of IFN-γ, IL-1, IL-2, IL-4, IL-6, IL-10, MSP/RON, HGF/Met systems, Treg lymphocytes were investigated. Results: In grafted untreated rats IFN-γ increased in serum and renal tissue and IL-6 rose in serum. MSC prevented both the phenomena, increased IL-10 serum levels and Treg number in the graft. Furthermore MSC increased serum and tissue HGF levels, Met tubular expression and prevented the suppression of tubular MSP/RON expression. Conclusions: Our results demonstrate that MSC modify cytokine network to a tolerogenic setting, they suppress Th1 cells, inactivate monocytes/macrophage, recruit Tregs. In addition, MSC sustain the expression of the Scatter Factor systems expression, i.e. systems that are committed to defend survival and stimulate regeneration of tubular cells.

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KW - Experimental model

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KW - Scatter factors

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