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Stem Cell Technology: Epigenetics, Genomics, Proteomics and Metabonomics
Article first published online: 12 FEB 2013
Copyright © 2012 AlphaMed Press
Volume 31, Issue 2, pages 317–326, February 2013
How to Cite
Nystedt, J., Anderson, H., Tikkanen, J., Pietilä, M., Hirvonen, T., Takalo, R., Heiskanen, A., Satomaa, T., Natunen, S., Lehtonen, S., Hakkarainen, T., Korhonen, M., Laitinen, S., Valmu, L. and Lehenkari, P. (2013), Cell Surface Structures Influence Lung Clearance Rate of Systemically Infused Mesenchymal Stromal Cells. STEM CELLS, 31: 317–326. doi: 10.1002/stem.1271
Author contributions: J.N.: conception and design (main contributor), collection and assembly of data (main contributor), data analysis and interpretation (main contributor), manuscript writing (main contributor), and final approval of manuscript; H.A.: conception and design, collection and assembly of data, data analysis and interpretation, and manuscript writing; J.T., M.P., T.H., R.T., A.H., T.S., S.N., S.I.L., and T.H.: collection and assembly of data, data analysis and interpretation, and manuscript writing; M.K.: administrative support, data interpretation, and manuscript writing; S.L.: conception and design, administrative support, and provision of study material; L.V.: conception and design, financial support, administrative support, data analysis and interpretation, and manuscript writing; P.L.: conception and design, financial support, provision of study material, collection and assembly of data, data analysis and interpretation, and manuscript writing. H.A., J.T., L.V., and P.L. contributed equally to this article.
Disclosure of potential conflicts of interest is found at the end of this article.
First published online in STEM CELLSEXPRESS November 6, 2012.
- Issue published online: 12 FEB 2013
- Article first published online: 12 FEB 2013
- Accepted manuscript online: 6 NOV 2012 11:33PM EST
- Manuscript Accepted: 13 OCT 2012
- Manuscript Received: 28 JUN 2012
- Tekes—the Finnish Funding Agency for Technology and Innovation
- Mesenchymal stromal/stem cell;
- Systemic infusion;
- Cell surface;
- Cell adherence;
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 α4 integrin (CD49d, VLA-4), α6 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. STEM CELLS2013;31:317–326