BackgroundRenal fibrosis is characterized by infiltration of interstitial inflammatory cells and release of inflammatory mediators, activation and proliferation of fibroblasts, and deposition of excessive extracellular matrix (ECM). The aim of this study was to evaluate the effect of human umbilical cord-derived mesenchymal stem cell (hucMSC) conditioned medium (CM) on renal tubulointerstitial inflammation and fibrosis.MethodsRenal interstitial fibrosis was prepared in vivo using the unilateral ureteral obstruction (UUO). Rats were divided randomly into Sham group, Sham group with CM, UUO group, and UUO group with CM. The effect of hucMSC-CM on kidney injury induced by UUO was assessed by detecting kidney histopathology, serum creatinine (SCr), and blood urea nitrogen (BUN). The levels of TNF-α, IL-6, and IL-1β in serum and kidney tissues were detected by ELISA. The expression of proteins associated with fibrosis and renal inflammation was investigated using immunohistochemical staining and western blotting. The effects of hucMSC-CM on the TGF-β1-induced epithelial–mesenchymal transition (EMT) process and on inflammation in NRK-52E cells were investigated by immunofluorescent staining, ELISA, and western blotting.ResultshucMSC-CM reduced extracellular matrix deposition and inflammatory cell infiltration as well as release of inflammatory factors in UUO-induced renal fibrosis. Furthermore, hucMSC-CM markedly attenuated the EMT process and proinflammatory cytokines in rats with UUO and TGF-β1-induced NRK-52E cells. hucMSC-CM also inhibited the TLR4/NF-κB signaling pathway in vivo and in vitro.ConclusionsOur results suggest that hucMSC-CM has protective effects against UUO-induced renal fibrosis and that hucMSC-CM exhibits its anti-inflammatory effects through inhibiting TLR4/NF-κB signaling pathway activation.Electronic supplementary materialThe online version of this article (doi:10.1186/s13287-017-0760-6) contains supplementary material, which is available to authorized users.

Bone Tumor TherapySignificant attention has been focused on bone tumor therapy recently. At present, the treatment in clinic typically requires surgical intervention. However, a few tumor cells remain around bone defects after surgery and subsequently proliferate within several days. Thus, fabrication of biomaterials with dual functions of tumor therapy and bone regeneration is significant. Herein, the injectable hydrogel containing cisplatin (DDP) and polydopamine-decorated nano-hydroxyapatite is prepared via Schiff base reaction between the aldehyde groups on oxidized sodium alginate and amino groups on chitosan. The hydrogel exhibits sustained release properties for DDP due to the immobilization of DDP via abundant functional groups on polydopamine (PDA). Additionally, given the intense absorption of PDA in the near-infrared region, the hydrogel exhibits excellent photothermal effects when exposed to the NIR laser (808 nm). Based on the properties, the hydrogel effectively ablates tumor cells (4T1 cells) in vitro and suppresses tumor growth in vivo. Furthermore, the hydrogel promotes the adhesion and proliferation of bone mesenchymal stem cells in vitro due to the abundant functional groups on PDA and further induces bone regeneration in vivo. Therefore, the study extends research on novel biomaterials with dual functions of tumor therapy and bone regeneration.

Recently, several studies have demonstrated that cancer cell-derived exosomes can facilitate tumor development and metastasis formation. However, the detailed function of exosomes released by cancer stem cells (CSCs) requires further investigation. The aim of the present study was to investigate the role of CSC-derived exosomes in tumor development. For this purpose, Piwil2-induced cancer stem cells (Piwil2-iCSCs) were used as exosome-generating cells, while fibroblasts (FBs) served as recipient cells. Exosomes were isolated by the ultracentrifugation of Piwil2-iCSC-conditioned medium and identified by transmission electron microscopy, nanoparticle tracking analysis and western blot analysis. To evaluate the effects of the exosomes on cell proliferation, migration and invasion, cell counting assay (CCK-8), a wound healing assay and a Transwell assay were performed. Protein expression [matrix metalloproteinase (MMP)2, MMP9, α-smooth muscle actin (α-SMA) and vimentin and fibroblast-activating protein (FAP)] was examined in FBs by western blot analysis. It was found that the Piwil2-iCSC-derived exosomes (Piwil2-iCSC-Exo) were oval or spherical, membrane-coated vesicles with a uniform size (30-100 nm in diameter). They are characterized by the surface expression of CD9, CD63, Hsp70 and Piwil2 proteins. Additional results from functional analyses revealed that Piwil2-iCSC-Exo enhanced the proliferative, migratory and invasive abilities of FBs, accompanied by the upregulated expression of MMP2 and MMP9. In addition, the increased expression of α-SMA (P<0.05), vimentin (P<0.01 vs. control group, P<0.05 vs. PBS group) and FAP (P<0.001 vs. control group, P<0.01 vs. PBS group) following exposure to Piwil2-iCSC-Exo suggested that the exosomes induced FB transformation into cancer-associated fibroblasts (CAFs). On the whole, the findings of this study demonstrate that Piwil2-iCSC-Exo induce the cancer-associated phenotype in fibroblasts in vitro, suggesting that CSCs can promote tumor development through the modulation of the tumor microenvironment.

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