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Official websites use. Share sensitive information only on official, secure websites. Mesenchymal stromal cells can ameliorate cisplatin-induced kidney injury. We hypothesize that the MSC secretome orchestrates the vicious cycle of injury and inflammation by acting on proximal tubule epithelial cells PTECs and macrophages individually, but further by counteracting their cellular crosstalk.
Second, the effects of cisplatin and the CM on macrophages were measured. Lastly, in an indirect co-culture system, the interplay between the two cell types was assessed.
Second, while cisplatin exerted only minor effects on macrophages, the CM skewed macrophage phenotypes to the anti-inflammatory M2-like phenotype and increased phagocytosis. Keywords: MSC secretome, proximal tubular epithelial cells, cisplatin, macrophages, acute kidney injury, oxidative stress, crosstalk, phagocytosis. Mesenchymal stromal cells MSCs are considered promising candidates for the development of cell-based therapies for a variety of diseases [ 1 ].
The underlying mechanism of action by which MSCs deliver those therapeutic benefits includes the release of bioactive paracrine factors, collectively regarded as the secretome [ 4 ]. In general, the MSC secretome consists of soluble factors, which include various growth factors, cytokines, hormones, chemokines, anti-oxidants, extracellular matrix proteins, and other serum proteins, and extracellular vesicles EVs.
Given its diverse contents, the MSC secretome presents an option for multimodal treatment for debilitating diseases, such as kidney injury [ 1 ]. Cis-diamminedichloroplatinum II cisplatin is an anti-cancer drug with a wide range of side effects, including gastrotoxicity, neurotoxicity, allergic reactions, and, most prevalent of all, nephrotoxicity [ 5 ]. Because of this, cisplatin-induced AKI has been the dose-limiting factor of cisplatin treatment, significantly compromising its efficacy in treating cancer [ 6 , 7 , 8 ].