Mesenchymal Stem Cells Attenuate Renal Fibrosis Through Immune Modulation and Remodeling Properties in a Rat Remnant Kidney Model

Abstract

Mesenchymal stem cells (MSCs) have regenerative properties in acute kidney injury, but their role in chronic kidney diseases is still unknown. More specifically, it is not known whether MSCs halt fibrosis. The purpose of this work was to investigate the role of MSCs in fibrogenesis using a model of chronic renal failure. MSCs were obtained from the tibias and femurs of male Wistar-EPM rats. Female Wistar rats were subjected to the remnant model, and 2|3|10 5 MSCs were intravenously administrated to each rat every other week for 8 weeks or only once and followed for 12 weeks. SRY gene expression was observed in female rats treated with male MSCs, and immune localization of CD73 1 CD90 1 cells at 8 weeks was also assessed. Serum and urine analyses showed an amelioration of functional parameters in MSC-treated animals at 8 weeks, but not at 12 weeks. Masson's trichrome and Sirius red staining demonstrated reduced levels of fibrosis in MSC-treated animals. These results were corroborated by reduced vimentin, type I collagen, transforming growth factor b, fibroblast specific protein 1 (FSP-1), monocyte chemoattractant protein 1, and Smad3 mRNA expression and a smooth muscle actin and FSP-1 protein expression. Renal interleukin (IL)-6 and tumor necrosis factor a mRNA expression levels were significantly decreased after MSC treatment, whereas IL-4 and IL-10 expression levels were increased. All serum cytokine expression levels were decreased in MSC-treated animals. Taken together, these results suggested that MSC therapy can indeed modulate the inflammatory response that follows the initial phase of a chronic renal injury. The immunosuppressive and remodeling properties of MSCs may be involved in the decreased fibrosis in the kidney.

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

“…[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.…”

Role of adipose tissue-derived stem cells in the progression of renal disease

“…The primary mechanism of action of adult stem cells is immunoregulation (23,24) . This occurs by means of a predominantly paracrine effect of the ADSCs, via a "touch and go" phenomenon in which these cells are attracted to the site of the lesion, secrete immune factors, and then leave that tissue or die.…”

“…Semedo et al demonstrated that the administration of mesenchymal stem cells (MSCs) improved histological and functional parameters, besides reducing fibrosis in a model of serious renal ablation. The renal protection resulting from the administration of MSCs also attenuated the chronic hypoxia, oxidative stress, and inflammatory cytokines that lead to EMT and are present during CRD (23,24) . Several other studies described the beneficial effects of ADSCs administration.…”

Chronic Kidney Disease: A Life Course Health Development Perspective

“…Reports of improvement in renal function in rat remnant kidney by injections of the mesenchyme make pursuit of stem cell technologies promising (Cavaglieri et al 2009;Semedo et al 2009). However, better understanding of the epigenetic and genetic factors regulating cell types may be necessary to program and tailor stem cells to renal compartments (Hendry and Little 2012).…”