Mesenchymal stem cell therapy promotes the improvement and recovery of renal function in a preclinical model

Abstract

Acute renal failure (ARF) is an extremely important public health issue in need of novel therapies. The present study aimed to evaluate the capacity of mesenchymal stem cell (MSC) therapy to promote the improvement and recovery of renal function in a preclinical model. Wistar rats were used as the experimental model, and our results show that cisplatin (5mg/kg) can efficiently induce ARF, as measured by changes in biochemical (urea and creatinine) and histological parameters. MSC therapy performed 24h after the administration of chemotherapy resulted in normalized plasma urea and creatinine levels 30 and 45d after the onset of kidney disease. Furthermore, MSC therapy significantly reduced histological changes (intratubular cast formation in protein overload nephropathy and tubular hydropic degeneration) in this ARF model. Thus, considering that current therapies for ARF are merely palliative and that MSC therapy can promote the improvement and recovery of renal function in this model system, we suggest that innovative/alternative therapies involving MSCs should be considered for clinical studies in humans to treat ARF.

Exosomal microRNAs derived from mesenchymal stem cells: cell-to-cell messages

“…The early mechanism of MSCs may be due to the production of soluble factors, such as nitric oxide [47], indoleamine 2,3-dioxygenase (IDO) [48], hepatocyte growth factor (HGF) [65], and transforming growth factor-β [46]. Moreover they may also exert immunosuppressive functions through direct cell-to-cell contact.…”

“…Some studies have suggested that MSCs have the innate ability to migrate to sites of inflammation and also to the tumor microenvironments. While all of the factors that contribute to MSC migration remain to be identified, research has suggested that MSC migration is caused by different chemokines and interplay with chemokine receptors, for example, stem cell factor (c-kit), HGF or c-Met [76], platelet derived growth factor (PDGF)/PDGF receptor [48,49], vascular endothelial growth factor (VEGF)/VEGF receptor [77], monocyte chemo-attractant protein-1 (MCP-1), C-C chemokine Type 2 receptors [46], high mobility group box 1, receptor for glycation end-products [78,79], stromal cell derived factor 1 (SDF-1), C-X-C chemokine Type 4 receptors (CXCR4) [47,48], as well as additional cell adhesion molecules (Fig. 2) [47,80].…”

“…MSCs also exert paracrine effects, and are antiinflammatory and immunomodulatory [43][44][45][46].. Currently, MSCs can be isolated from different sources and have been employed as therapeutic approaches to treat several diseases and injuries [43][44][45][46][47][48][49][50][51]. However, many studies have concluded that MSCs were not easily engrafted into the target tissue as had initially been proposed; therefore, their benefit in tissue repair may be more due to their transient effects on the surrounding tissues.…”

Renal disease pathophysiology and treatment: contributions from the rat

“…The potential of bone-marrow-derived MSCs to accelerate healing has been demonstrated in several rat models of hypertension (as discussed above) and of renal disease, including in the anti-Thy1.1 model (Li et al, 2006), the 5/6th nephrectomy model of progressive CKD (Cavaglieri et al, 2009; Choi et al, 2009) and in an AKI model induced by cisplatin (Urt-Filho et al, 2016). MSCs might reverse AKI by a paracrine mechanism rather than by MSC transdifferentiation.…”

Vitamin D: Correlation with biochemical and body composition changes in a southern Brazilian population and induction of cytotoxicity in mesenchymal stem cells derived from human adipose tissue

“…The differentiation medium was changed every 72 h [49,50], and the differentiation process lasted 14 days [51,52].…”