Stem cells
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Preclinical studies using bone marrow derived cells to treat traumatic brain injury have demonstrated efficacy in terms of blood-brain barrier preservation, neurogenesis, and functional outcomes. Phase 1 clinical trials using bone marrow mononuclear cells infused intravenously in children with severe traumatic brain injury demonstrated safety and potentially a central nervous system structural preservation treatment effect. This study sought to confirm the safety, logistic feasibility, and potential treatment effect size of structural preservation/inflammatory biomarker mitigation in adults to guide Phase 2 clinical trial design. ⋯ There appears to be a treatment signal as evidenced by central nervous system structural preservation, consistent with previous pediatric trial data. Inflammatory biomarkers are downregulated after cell infusion. Stem Cells 2016 Video Highlight: https://youtu.be/UiCCPIe-IaQ Stem Cells 2017;35:1065-1079.
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Mesenchymal stem cells (MSC) are multipotent cells able to differentiate into several cell types, hence providing cell reservoirs for therapeutic applications. The absence of detectable MSC homing at injury sites suggests that paracrine functions could, at least in part, be mediated by extracellular vesicles (EVs); EVs are newly identified players that are studied mainly as predictive or diagnostic biomarkers. Together with their clinical interests, EVs have recently come to the fore for their role in cell-to-cell communication. ⋯ In the paradigm where EVs act as bioeffectors educating target cells, we demonstrated that kidney tubular cells lacking IL-10 expression and exposed to BMMSC-EVs and CBMSC-EVs acquired the IL-10 mRNA, which was efficiently translated into the corresponding protein. These findings suggest that horizontal mRNA transfer through EVs is a new mechanism in the MSC restoring ability observed in vivo that is here further demonstrated in an in vitro rescue model after acute cisplatin injury of tubular cells. Stem Cells 2017;35:1093-1105.