Original Research Article
Mesenchymal stem cells contribute to endogenous FVIII:c production
Article first published online: 28 JAN 2013
Copyright © 2012 Wiley Periodicals, Inc.
Journal of Cellular Physiology
Volume 228, Issue 5, pages 1010–1016, May 2013
How to Cite
Sanada, C., Kuo, C.-J., Colletti, E. J., Soland, M., Mokhtari, S., Knovich, M. A., Owen, J., Zanjani, E. D., Porada, C. D. and Almeida-Porada, G. (2013), Mesenchymal stem cells contribute to endogenous FVIII:c production. J. Cell. Physiol., 228: 1010–1016. doi: 10.1002/jcp.24247
- Issue published online: 28 JAN 2013
- Article first published online: 28 JAN 2013
- Accepted manuscript online: 5 OCT 2012 07:48AM EST
- Manuscript Accepted: 26 SEP 2012
- Manuscript Received: 19 AUG 2011
- National Institutes of Health. Grant Numbers: HL73737, HL97623
Besides the liver, it has been difficult to identify which organ(s) and/or cellular component(s) contribute significantly to the production of human FVIII:c (FVIII). Thus far, only endothelial cells have been shown to constitute a robust extrahepatic source of FVIII, possibly explaining both the diverse presence of FVIII mRNA in the body, and the observed increase in FVIII levels during liver failure. Here, we investigate whether human mesenchymal stem cells (MSC), ubiquitously present in different organs, could also contribute to FVIII production. MSC isolated from human lung, liver, brain, and bone marrow expressed FVIII message as determined by quantitative-RT-PCR. Using an antibody specific for FVIII, confocal microscopy, and umbilical cord-derived endothelial cells (HUVEC) as a negative control, we demonstrated that, in MSC, FVIII protein was not stored in granules; rather, it localized to the perinuclear region. Furthermore, functional FVIII was detected in MSC supernatants and cell lysates by aPTT and chromogenic assays. These results demonstrate that MSC can contribute at low levels to the functional FVIII pool, and advance the understanding of the physiology of FVIII production and secretion. J. Cell. Physiol. © 2012 Wiley Periodicals, Inc.