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ADIPOSE TISSUE-DERIVED STEM CELL TREATMENT PREVENTS RENAL DISEASE PROGRESSION
Authors: Cassiano Donizetti-Oliveira, Patricia Semedo, Marina Burgos-Silva, Marco Antonio Cenedeze, Denise Maria Avancini Costa Malheiros, Marlene A. Reis , Alvaro Pacheco-Silva, Niels Olsen Saraiva Câmara
Source: Cell Transplantation
Publisher: Cognizant Communication Corporation
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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, 2x10⁵ ASCs were intraperitoneally administered, and mice were followed for 24 h post-treatment and then at some other time interval for the next 6 weeks. Also, animals were treated with 2x10⁵ ASCs at six 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-α, KC, RANTES and IL-1α. 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.Document Type:
DOI: http://dx.doi.org/10.3727/096368911X623925
Appeared or available online: February 2, 2012
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