Adipose Tissue-Derived Stem Cell Treatment Prevents Renal Disease Progression

Adipose Tissue-Derived Stem Cell Treatment Prevents Renal Disease Progression

Author Donizetti-Oliveira, Cassiano Autor UNIFESP Google Scholar
Semedo, Patricia Autor UNIFESP Google Scholar
Burgos-Silva, Marina Autor UNIFESP Google Scholar
Cenedeze, Marco Antonio Autor UNIFESP Google Scholar
Malheiros, Denise Maria Avancini Costa Google Scholar
Reis, Marlene A. Google Scholar
Pacheco-Silva, Alvaro Autor UNIFESP Google Scholar
Câmara, Niels Olsen Saraiva Autor UNIFESP Google Scholar
Institution Universidade Federal de São Paulo (UNIFESP)
Universidade de São Paulo (USP)
Univ Fed Triangulo Mineiro
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.
Keywords Adipose-derived stem cell
Acute kidney injury
Ischemia-reperfusion injury
Fibrosis
Inflammation
Language English
Sponsor Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
DECIT/Ministerio do Saude
Complex Fluids INCT
Grant number FAPESP: 09/13251-6
FAPESP: 07/07139-3
CNPq: 473844/2009-5
Date 2012-01-01
Published in Cell Transplantation. Putnam Valley: Cognizant Communication Corp, v. 21, n. 8, p. 1727-1741, 2012.
ISSN 0963-6897 (Sherpa/Romeo, impact factor)
Publisher Cognizant Communication Corp
Extent 1727-1741
Origin http://dx.doi.org/10.3727/096368911X623925
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000311597400011
URI http://repositorio.unifesp.br/handle/11600/34404

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