Key Points We established hypoxia-resistant cells that can mimic in vivo conditions of hypoxic bone marrow. Exosomal miR-135b derived from these cell lines enhanced endothelial tube formation under hypoxia via the HIF-FIH signaling pathway.

Key Points• Exosomal miR-340 derived from young BMSCs inhibited tumor angiogenesis via the HGF/c-MET signaling pathway.• The anti-angiogenic effect of exosomes from older BMSCs was restored by direct transfection of young BMSC-derived exosomal miRNAs.The study of bone marrow stromal cells (BMSCs) and the exosomes they secrete is considered promising for cancer therapy. However, little is known about the effect of donor age onBMSCs. In the present study, we investigated the therapeutic potential of BMSC exosomes derived from donors of different ages using an in vivo model of hypoxic bone marrow in multiple myeloma (MM). We found that donor age was strongly related to senescent changes

BackgroundWe undertook a study to evaluate the clinical relevance of miR-92a in plasma obtained from non-Hodgkin's lymphoma (NHL) patients, because the miR-17-92 polycistronic miRNA cluster plays a crucial role in lymphomagenesis and affects neo-angiogenesis.Methodology/Principal FindingsPlasma miR-92a values in NHL were extremely low (<5%), compared with healthy subjects (P<.0001), irrespective of lymphoma sub-type. The very low plasma level of miR-92a increased in the complete response (CR) phase but did not reach the normal range, and the plasma level was lower again in the relapse phase. Patients in CR or CR unconfirmed with a plasma miR-92a level of less than the cut-off level showed a significantly high relapse rate compared with patients with normalized plasma miR-92a level.Conclusions/SignificanceThe current results therefore indicate that the plasma miR-92a value could be a novel biomarker not only for diagnosis but also for monitoring lymphoma patients after chemotherapy.

Recent studies have demonstrated that one-third of known microRNAs (miRNAs) are stably detectable in plasma. Therefore, we assessed plasma miRNAs to investigate the dynamics of oncomir 17-92a, which is highly expressed in multiple myeloma (MM) patients. The plasma miR-92a level in symptomatic MM patients was significantly downregulated compared with normal subjects (P<0.0001), regardless of immunoglobulin subtypes or disease stage at diagnosis. In contrast, miR-92a levels in peripheral blood CD8+ or CD4+ cells from MM patients were lower than those of normal subjects, and the miR-92a levels of the cells tended to correlate with plasma miR-92a levels. The plasma miR-92a level in the complete remission group became normalized, whereas the partial response (PR) and very good PR groups did not reach the normal range. In smoldering MM, the plasma miR-92a level did not show a significant difference compared with normal subjects. Our findings suggest that measurement of the plasma miR-92a level in MM patients could be useful for initiation of chemotherapy and monitoring disease status, and the level may represent, in part, the T-cell immunity status of these patients.

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