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  • ISSN: 2379-0490
    Current Issue
    Volume 3, Issue 2
    Research Article
    Josef Maertz, Maximilian Michael Saller, Kallukalam Bobby Cherian, Denitsa Docheva, Matthias Schieker, Elias Volkmer*
    Abstract: Human mesenchymal stem cells display a high self-renewing potential and are capable of differentiating along the osteogenic lineage if stimulated accordingly. Therefore they are suitable for cell-based therapies to regenerate bone tissue. However, oxygen conditions of in vitro cultures (normally 21% pO2) and the bone marrow, as the natural niche of hMSC, with physiologic oxygen tensions between 2-5% pO2 differ widely. Similarly, in the site of fracture, hMSC are exposed to acute hypoxia. Recent studies suggested that hypoxia inducible factor 1 alpha, a key transcription factor regulating cell metabolism under hypoxic conditions, may play a role in the process of osteogenic differentiation in vivo. The goal of this study was to assess the impact of hypoxia and hypoxia inducible factor 1 alpha regulation on proliferation and osteogenic differentiation of hMSC in vitro.
    hMSCs were cultured under conditions of 21% pO2 (normoxia), 2% pO2 (hypoxia) and 0% pO2 (anoxia). The oxygen concentration was detected by fluorimetric oxygen measurement. Hypoxia inducible factor 1 alpha was down regulated by silencing-RNA-technique under hypoxia, or stabilized with desferrioxamine under normoxia, and subsequently prepared on mRNA- as well as on protein level. The amount of osteogenic differentiation was measured by quantitative Alizarin-Red-Staining.
    Our results show that mRNA-expression of HIF-1α is independent of the surrounding oxygen concentrations. Within anoxic and hypoxic conditions, HIF-1α-protein was detectable abundantly, whereas it was degraded rapidly under normoxic conditions. HIF-1α-downregulation did not change osteogenic differentiation under hypoxic conditions in vitro. We were able to demonstrate that proliferation of hMSC is not impaired by low oxygen concentrations, whereas hypoxia inhibits the osteogenic differentiation of hMSC. This suggests that among further factors also hypoxia might contribute to maintain the stem cell properties in hMSC. As hypoxic conditions are more physiologic for hMSC, we suggest that the expansion of osteo-progenitor-cells should preferentially take place in low oxygen atmospheres.
    Mini Review
    Joseph A ZULLO, May M RABADI, Rishikesh MOREY, Michael S GOLIGORKSY, Brian B RATLIFF
    Abstract: Stem cell therapy is proving to be an effective treatment option for a variety of injuries and diseases. Despite the promise of this therapy, much remains unknown about this field. More research is still required to unlock the full potential of stem cell therapy and its use for repair of damaged organs and tissues. Different approaches are being addressed to continually maximize the beneficial effects of stem cells. One such approach is the simultaneous co-delivery of two different stem celltypes instead of their individual delivery, such as co-delivery of exogenous MSCs with EPCs. MSCspossess immunomodulatory properties and enhance healing of various epithelial and stromatissues. In turn, EPCs mediate angiogenesis and repair of microvascular structures. Both of these stem cells mediate much of their effects through paracrine signaling mechanisms. While delivered individually these cells possess significant reparative benefits, delivering these cells together may synergistically enhance these effects. This review will summarize the investigations conducted thus far using co-delivery of MSCs and EPCs for treatment of injuries across multiple fields' includingmyocardial infarction, bone regeneration after fracture, acute kidney injury and vascular injury.
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