Adipose Tissue-Derived Stem Cell Treatment Prevents Renal Disease Progression

Author(s)

Donizetti-Oliveira, Cassiano ^[1] ; Semedo, Patricia ^[1] ; Burgos-Silva, Marina ^[1] ; Cenedeze, Marco Antonio ^[1] ; Avancini Costa Malheiros, Denise Maria ^[2] ; Reis, Marlene A. ^[3] ; Pacheco-Silva, Alvaro ^[1] ; Saraiva Camara, Niels Olsen ^{[1, 4]}

Affiliation

^[1] Univ Fed Sao Paulo, Div Nephrol, Escola Paulista Med, Expt & Clin Immunol Lab, BR-04023900 Sao Paulo - Brazil

^[2] Univ Sao Paulo, Dept Pathol, Sao Paulo - Brazil

^[3] Univ Fed Triangulo Mineiro, Div Pathol, Uberaba, MG - Brazil

^[4] Univ Sao Paulo, Dept Immunol, Lab Transplantat Immunobiol, Sao Paulo - Brazil

• Document type: Journal article
• Source: CELL TRANSPLANTATION; v. 21, n. 8, p. 1727-1741, 2012.
• Web of Science Citations: 43

Abstract

Adipose tissue-derived stem cells (ASCs) are an attractive source of stem cells with regenerative properties that are similar to those of bone marrow stem cells. Here, we analyze the role of ASCs in reducing the progression of kidney fibrosis. Progressive renal fibrosis was achieved by unilateral clamping of the renal pedicle in mice for 1 h; after that, the kidney was reperfused immediately. Four hours after the surgery, 2 x 10(5) ASCs were intraperitoneally administered, and mice were followed for 24 h posttreatment and then at some other time interval for the next 6 weeks. Also, animals were treated with 2 x 10(5) ASCs at 6 weeks after reperfusion and sacrificed 4 weeks later to study their effect when interstitial fibrosis is already present. At 24 h after reperfusion, ASC-treated animals showed reduced renal dysfunction and enhanced regenerative tubular processes. Renal mRNA expression of IL-6 and TNF was decreased in ASC-treated animals, whereas IL-4. IL-10, and HO-1 expression increased despite a lack of ASCs in the kidneys as determined by SRY analysis. As expected, untreated kidneys shrank at 6 weeks, whereas the kidneys of ASC-treated animals remained normal in size, showed less collagen deposition, and decreased staining for FSP-1, type I collagen, and Hypoxyprobe. The renal protection seen in ASC-treated animals was followed by reduced serum levels of TNF-alpha, KC, RANTES, and IL-1 alpha. Surprisingly, treatment with ASCs at 6 weeks, when animals already showed installed fibrosis, demonstrated amelioration of functional parameters, with less tissue fibrosis observed and reduced mRNA expression of type I collagen and vimentin. ASC therapy can improve functional parameters and reduce progression of renal fibrosis at early and later times after injury, mostly due to early modulation of the inflammatory response and to less hypoxia, thereby reducing the epithelial-mesenchymal transition. (AU)

• FAPESP's process: 07/07139-3 - The role of heme oxygenase 1 in different renal inflammatory process in experimental animal models
• Grantee: Niels Olsen Saraiva Câmara
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 09/13251-6 - Role of stem cells derived from adipose tissue in the progression of renal disease
• Grantee: Cassiano Donizetti de Oliveira
• Support Opportunities: Scholarships in Brazil - Master