title: Mesenchymal stromal cells reset the scatter factor system and cytokine network in experimental kidney transplantation.
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.
authors.affiliation: Unit of Nephrology, Dialysis and Transplantation, Fondazione, IRCCS Policlinico San Matteo and University of Pavia, viale Golgi 19, Pavia, 27100, Italy. mgregorini@hotmail.com.
authors.forename: Marilena
authors.initials: M
authors.lastname: Gregorini
authors.forename: Francesca
authors.initials: F
authors.lastname: Bosio
authors.forename: Chiara
authors.initials: C
authors.lastname: Rocca
authors.forename: Valeria
authors.initials: V
authors.lastname: Corradetti
authors.forename: Teresa
authors.initials: T
authors.lastname: Valsania
authors.forename: Eleonora Francesca
authors.initials: EF
authors.lastname: Pattonieri
authors.forename: Pasquale
authors.initials: P
authors.lastname: Esposito
authors.forename: Giulia
authors.initials: G
authors.lastname: Bedino
authors.forename: Chiara
authors.initials: C
authors.lastname: Collesi
authors.forename: Carmelo
authors.initials: C
authors.lastname: Libetta
authors.forename: Francesco
authors.initials: F
authors.lastname: Frassoni
authors.forename: Antonio
authors.initials: A
authors.lastname: Dal Canton
authors.forename: Teresa
authors.initials: T
authors.lastname: Rampino
mesh_terms: D064591:Allografts; D000818:Animals; D049109:Cell Proliferation; D016207:Cytokines / Q000097:blood / Q000378:metabolism*; D051858:Forkhead Transcription Factors / Q000378:metabolism; D017228:Hepatocyte Growth Factor / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D016030:Kidney Transplantation; D007684:Kidney Tubules / Q000473:pathology; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D009000:Monocytes / Q000378:metabolism; D009336:Necrosis; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: D016207:Cytokines; D051858:Forkhead Transcription Factors; C500522:Foxp3 protein, rat; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; C082332:macrophage stimulating protein; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met; C080835:RON protein; D020794:Receptor Protein-Tyrosine Kinases