title: Early modulation of inflammation by mesenchymal stem cell after acute kidney injury.
abstract: Therapy with stem cells has showed to be promising for acute kidney injury (AKI), although how it works is still controversial. Modulation of the inflammatory response is one possible mechanism. Most of published data relies on early time and whether the protection is still maintained after that is not known. Here, we analyzed whether immune modulation continues after 24 h of reperfusion. MSC were obtained from male Wistar rats. After 3-5 passages, cells were screened for CD73, CD90, CD44, CD45, CD29 and CD 31. In addition, MSC were submitted to differentiation in adipocyte and in osteocyte. AKI was induced by bilaterally clamping of renal pedicles for 60 min. Six hours after injury, MSC (2 x 10(5) cells) were administered intravenously. MSC-treated animals presented the lowest serum creatinine compared to non-treated animals (24 h: 1.3+/-0.21 vs. 3.23+/-0.89 mg/dl, p<0.05). The improvement in renal function was followed by a lower expression of IL-1b, IL-6 and TNF-alpha and higher expression of IL-4 and IL-10. However, 48 h after reperfusion, this cytokine profile has changed. The decrease in Th1 cytokines was less evident and IL-6 was markedly up regulated. PCNA analysis showed that regeneration occurs faster in kidney tissues of MSC-treated animals than in controls at 24 h. And also ratio of Bcl-2/Bad was higher at treated animals after 24 and 48 h. Our data demonstrated that the immunomodulatory effects of MSC occur at very early time point, changing the inflammation profile toward a Th2 profile.
authors.affiliation: Division of Nephrology, Federal University of São Paulo, São Paulo (UNIFESP), Brazil.
authors.forename: Patricia
authors.initials: P
authors.lastname: Semedo
authors.forename: Carolina G
authors.initials: CG
authors.lastname: Palasio
authors.forename: Cassiano D
authors.initials: CD
authors.lastname: Oliveira
authors.forename: Carla Q
authors.initials: CQ
authors.lastname: Feitoza
authors.forename: Giselle M
authors.initials: GM
authors.lastname: Gonçalves
authors.forename: Marcos Antonio
authors.initials: MA
authors.lastname: Cenedeze
authors.forename: Pamella M H
authors.initials: PM
authors.lastname: Wang
authors.forename: Vicente P A
authors.initials: VP
authors.lastname: Teixeira
authors.forename: Marlene A
authors.initials: MA
authors.lastname: Reis
authors.forename: Alvaro
authors.initials: A
authors.lastname: Pacheco-Silva
authors.forename: Niels Olsen Saraiva
authors.initials: NO
authors.lastname: Câmara
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation / Q000276:immunology; D003404:Creatinine / Q000097:blood; D004195:Disease Models, Animal; D007249:Inflammation / Q000276:immunology / Q000601:surgery; D053583:Interleukin-1beta / Q000276:immunology / Q000378:metabolism; D015850:Interleukin-6 / Q000276:immunology / Q000378:metabolism; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000276:immunology*; D010011:Osteocytes / Q000166:cytology / Q000378:metabolism; D018809:Proliferating Cell Nuclear Antigen / Q000276:immunology / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000276:immunology / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D051437:Renal Insufficiency / Q000276:immunology / Q000601:surgery*; D018418:Th2 Cells / Q000276:immunology*; D051025:bcl-Associated Death Protein / Q000276:immunology / Q000378:metabolism
chemical_list: C494821:Bad protein, rat; D053583:Interleukin-1beta; D015850:Interleukin-6; D018809:Proliferating Cell Nuclear Antigen; D019253:Proto-Oncogene Proteins c-bcl-2; D051025:bcl-Associated Death Protein; D003404:Creatinine