Abstract
The therapeutic action of bone marrow-derived mesenchymal stem cells (BMSCs) in acute kidney injury (AKI) has been reported by several groups. However, recent studies indicated that BMSCs homed to kidney tissues at very low levels after transplantation. The lack of specific homing of exogenously infused cells limited the effective implementation of BMSC-based therapies. In this study, we provided evidence that the administration of BMSCs combined with muscone in rats with gentamicin-induced AKI intravenously, was a feasible strategy to drive BMSCs to damaged tissues and improve the BMSC-based therapeutic effect. The effect of muscone on BMSC bioactivity was analyzed in vitro and in vivo. The results indicated that muscone could promote BMSC migration and proliferation. Some secretory capacity of BMSC still could be improved in some degree. The BMSC-based therapeutic action was ameliorated by promoting the recovery of biochemical variables in urine or blood, as well as the inhibition of cell apoptosis and inflammation. In addition, the up-regulation of CXCR4 and CXCR7 expression in BMSCs could be the possible mechanism of muscone amelioration. Thus, our study indicated that enhancement of BMSCs bioactivities with muscone could increase the BMSC therapeutic potential and further developed a new therapeutic strategy for the treatment of AKI.
Highlights
Acute kidney injury (AKI) is the rapid deterioration of renal function
Our study showed that bone marrow derived mesenchymal stem cells (BMSCs) combined with muscone was a feasible strategy in promoting BMSC migration, proliferation, and secretory capacity to repair kidney tissues in the rat model of gentamicin-induced AKI
The BMSCs used in our study were positive for CD29 (95.6%), CD44 (92.1%), CD73 (96.6%), CD90 (94.7%), CD105 (97.3%), and CD166 (88.2%), and nearly negative for CD14 (0.79%), CD34 (0.95%) and CD45 (1.64%), which were regared as the specific markers of hematopoietic cells (Figure 1A)
Summary
Acute kidney injury (AKI) is the rapid deterioration of renal function. It can be induced by numerous insults, and has high morbidity and mortality rates [1,2,3]. Different types of stem cells, such as amniotic fluid stem cells [16], hematopoietic progenitor cells [17], and kidney-derived mesenchymal stem cells[18], have been investigated, and their therapeutic effects in AKI treatment have been determined. For the action of bone marrow derived mesenchymal stem cells (BMSCs), several studies have used BMSCs to treat AKI in animal models and their results showed that renal function and structure could be improved with the infusion of BMSCs [19,20,21]. Compared with other stem cells, BMSCs are feasible in autologous treatment because of their source, number, and safety [21,22]
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