Adipose Tissue-Derived Stem Cell Treatment Prevents Renal Disease Progression

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 ´ 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 ´ 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, ASCtreated 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-a, KC, RANTES, and IL-1a. 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.

Interleukin-10 deficiency aggravates kidney inflammation and fibrosis in the unilateral ureteral obstruction mouse model

“…Western blotting was performed as previously described. 22,30 The primary antibodies were obtained from the following sources: anti-phospho-p65 (no. 3039), anti-phospho-Smad3 (no.…”

“…[13][14][15] In the context of kidney, IL-10 has been reported to effectively suppress the progression of acute and chronic renal damage in vivo. [16][17][18][19][20][21][22] However, the role of IL-10 in renal tubulointerstitial fibrosis has not been studied. Here, we used IL-10 À / À mice [23][24][25][26] with unilateral ureteral obstruction (UUO), a well-established model for kidney fibrosis, to investigate the roles of IL-10 in the progression of renal fibrosis.…”

Polycaprolactone nanofibrous mesh reduces foreign body reaction and induces adipose flap expansion in tissue engineering chamber

“…53,54 Over the long term, the acute inflammatory reaction manifests as a chronic pattern because the chamber acts as a nonremovable injury stimulation.…”

Topical Application of Adipose Tissue-Derived Mesenchymal Stem Cells Ameliorates Renal Ischemia-Reperfusion Injury in Rats

“…Although most of the topically applied MSCs were observed to be remained on the surface of the recipient kidney in our study, the potential biological roles of these MSC should not be overlooked. It was postulated these MSCs might execute their biologic roles via paracrine and/or endocrine pathways, including mitogenic, antiapopotic, anti-inflammatory and angiogenic effects to support the regeneration of local kidney cells [8,9,26,41,42]. In fact, from our study, we had demonstrated downregulation of the expressions of caspase-3 (indicator of apoptosis) and endothelin-1 (indicator of endothelial damage), and upregulation of the expression of NQO-1 (anti-oxidative marker) in kidneys treated with topical MSCs.…”

“…Renoprotective effects have been shown in preclinical studies [8][9][10][11][12][13]. It is believed that MSCs ameliorate renal injury by direct differentiation into tubular epithelial cells or by the release of paracrine/ endocrine factors that restore renal structure and function [8,9].…”