Experimental cell research
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Glioblastoma is the most common brain tumor. Median survival in unselected patients is <10 months. The tumor harbors stem-like cells that self-renew and propagate upon serial transplantation in mice, although the clinical relevance of these cells has not been well documented. ⋯ We found that canonical Wnt-signaling plays an important role in GSCs, but not in adult human neural stem cells. As well we identified a 30-gene signature highly overexpressed in GSCs. The expression of these signature genes correlates with clinical outcome and demonstrates the clinical relevance of GSCs.
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Mesenchymal stem cells (MSCs) secrete paracrine factors that could be cytoprotective and serve roles in immunoregulation during tissue injury. Although MSCs express HIV receptors, and co-receptors, and are susceptible to HIV infection, whether HIV-1 may affect biological properties of MSCs needs more study. We evaluated cellular proliferation, differentiation and paracrine functions of MSCs isolated from compact bones of healthy control mice and Tg26 HIV-1 transgenic mice. ⋯ Also, Tg26 HIV-1 MSCs secreted multiple cytokines, but at significantly lower levels than healthy MSCs, which resulted in failure of conditioned medium from these MSCs to protect cultured renal tubular cells from cisplatin toxicity. Therefore, HIV-1 had adverse biological effects on MSCs extending to their proliferation, differentiation, function, and therapeutic potential. These findings will help in advancing mechanistical insight in renal injury and repair in the setting of HIV-1 infection.