Abstract
IntroductionStudies have shown that stem cells exert their therapeutic effects on acute kidney injury (AKI) through paracrine/endocrine actions. If the protective effect is mediated in an endocrine manner, the injection of the factors that these cells secrete could be effective, but the effect of conditioned medium (CM) remains controversial.MethodsIn this study, we cultured mesenchymal stem cells (MSCs) and then transplanted them into an ischemia-reperfusion (I/R) injury model. CM was also injected into mice, and the histological changes, level of cell proliferation, loss of peritubular capillaries and anti-inflammatory and anti-apoptotic effects were examined at different time points.ResultsThe results showed that MSC infusion improved renal function and histological alterations, leading to significantly reduced mortality. MSC administration also promoted kidney microvasculature repair, attenuated kidney peritubular capillary loss, increased the proliferation of parenchymal cells and decreased CD68-positive macrophage infiltration and apoptotic cells. Although we determined that CM contained proangiogenic factors, including hepatocyte growth factor (HGF), vascular endothelial growth factor-A (VEGF-A) and insulin-like growth factor-1 (IGF-1), no favorable effects were observed during the course of repair.ConclusionsOur data show that MSC infusion promotes kidney repair in a variety of ways, including enhancement of the repair of peritubular capillaries and tubular epithelial cells and anti-inflammatory and anti-apoptotic effects. MSCs can secrete high levels of proangiogenic growth factors, but CM results in a nonsignificant improvement, indicating that MSCs play a role in kidney repair through paracrine rather than endocrine mechanisms. These results indicate that MSC infusion is a promising therapeutic strategy for promoting kidney repair after injury.Electronic supplementary materialThe online version of this article (doi:10.1186/scrt489) contains supplementary material, which is available to authorized users.
Highlights
Studies have shown that stem cells exert their therapeutic effects on acute kidney injury (AKI) through paracrine/endocrine actions
Conditioned medium contains the growth factors hepatocyte growth factor (HGF), vascular endothelial growth factor-A (VEGF-A) and insulin-like growth factor-1 (IGF-1) First, we examined the number of Mesenchymal stem cell (MSC) cultured with serum-free Dulbecco’s modified Eagle’s medium (DMEM) for 24, 48 and 72 hours
To investigate the mechanisms by which MSCs repair AKI, we determined whether the growth factors HGF, VEGF-A and IGF-1 were present in conditioned medium (CM)
Summary
Studies have shown that stem cells exert their therapeutic effects on acute kidney injury (AKI) through paracrine/endocrine actions. Mesenchymal stem cell (MSC)-based therapy holds great promise for treating immune disorders and for regenerative medicine, and promising results have been reported for the application of different types of stem cells in the Increasing studies have indicated that the beneficial effects of stem cells are primarily mediated via the paracrine/endocrine action of mediators rather than the direct differentiation and substitution of damaged cells [11,12,13,14], and many studies have shown that MSCs can secrete a wide range of growth factors and mediators that can suppress local immunologic reactions and inhibit fibrosis and apoptosis [2,12,15,16] According to these data, the direct injection of the supernatant from cultured MSCs may have beneficial effects on kidney repair. We observed that MSCs but not CM contributed to vascular regeneration, functional recovery, decreased macrophage infiltration and apoptotic cells and promoted survival
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