The promising clinical effects of mesenchymal stromal/ stem cells (MSCs) rely especially on paracrine and nonimmunogenic mechanisms. Delivery routes are essential for the efficacy of cell therapy and systemic delivery by infusion is the obvious goal for many forms of MSC therapy. Lung adhesion of MSCs might, however, be a major obstacle yet to overcome. Current knowledge does not allow us to make sound conclusions whether MSC lung entrapment is harmful or beneficial, and thus we wanted to explore MSC lung adhesion in greater detail. We found a striking difference in the lung clearance rate of systemically infused MSCs derived from two different clinical sources, namely bone marrow (BM-MSCs) and umbilical cord blood (UCB-MSCs). The BM-MSCs and UCB-MSCs used in this study differed in cell size, but our results also indicated other mechanisms behind the lung adherence. A detailed analysis of the cell surface profiles revealed differences in the expression of relevant adhesion molecules. The UCB-MSCs had higher expression levels of a4 integrin (CD49d, VLA-4), a6 integrin (CD49f, VLA-6), and the hepatocyte growth factor receptor (c-Met) and a higher general fucosylation level. Strikingly, the level of CD49d and CD49f expression could be functionally linked with the lung clearance rate. Additionally, we saw a possible link between MSC lung adherence and higher fibronectin expression and we show that the expression of fibronectin increases with MSC culture confluence. Future studies should aim at developing methods of transiently modifying the cell surface structures in order to improve the delivery of therapeutic cells.
US, MR imaging and MR sialography with modern technology have reached such a good accuracy in visualizing glandular structural changes that they are promising alternatives to the conventional invasive examinations in the diagnostics of SS.
The degree of local synovial inflammation at baseline, evaluated by dynamic and static MRI and quantitative NC scintigraphy, is closely related to the progression of wrist joint erosions during the first 2 yrs of the disease. Furthermore, at follow-up, if no persistent clinical response is achieved, these imaging methods may help to predict future erosiveness and help in clinical therapeutic decision making.
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