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Article first published online: 19 DEC 2012
Copyright © 2012 AlphaMed Press
Volume 31, Issue 1, pages 104–116, January 2013
How to Cite
Rodrigues, M., Blair, H., Stockdale, L., Griffith, L. and Wells, A. (2013), Surface Tethered Epidermal Growth Factor Protects Proliferating and Differentiating Multipotential Stromal Cells from FasL-Induced Apoptosis. STEM CELLS, 31: 104–116. doi: 10.1002/stem.1215
Author contributions: M.R.: conception and design, performed research, data analysis and interpretation, and wrote manuscript; H.B.: data analysis and image processing; L.S.: prepared tEGF surfaces; L.G.: conception and design, data interpretation, and financial support; A.W.: conception and design, data interpretation, edited manuscript, and financial support.
Disclosure of potential conflicts of interest is found at the end of this article.
First published online in STEM CELLSEXPRESS September 4, 2012.
- Issue published online: 19 DEC 2012
- Article first published online: 19 DEC 2012
- Accepted manuscript online: 4 SEP 2012 10:02AM EST
- Manuscript Accepted: 25 JUL 2012
- Manuscript Received: 8 MAY 2012
- National Institute of General Medical Sciences
- National Institute of Dental and Craniofacial Research. Grant Numbers: GM069668, DE019523
- Epidermal growth factor;
- Mesenchymal stem cells;
- Multipotential stromal cells;
Multipotential stromal cells or mesenchymal stem cells (MSCs) have been proposed as aids in regenerating bone and adipose tissues, as these cells form osteoblasts and adipocytes. A major obstacle to this use of MSC is the initial loss of cells postimplantation. This cell death in part is due to ubiquitous nonspecific inflammatory cytokines such as FasL generated in the implant site. Our group previously found that soluble epidermal growth factor (sEGF) promotes MSC expansion. Furthermore, tethering EGF (tEGF) onto a two-dimensional surface altered MSC responses, by restricting epidermal growth factor receptor (EGFR) to the cell surface, causing sustained activation of EGFR, and promoting survival from FasL-induced death. sEGF by causing internalization of EGFR does not support MSC survival. However, for tEGF to be useful in bone regeneration, it needs to allow for MSC differentiation into osteoblasts while also protecting emerging osteoblasts from apoptosis. tEGF did not block induced differentiation of MSCs into osteoblasts, or adipocytes, a common default MSC-differentiation pathway. MSC-derived preosteoblasts showed increased Fas levels and became more susceptible to FasL-induced death, which tEGF prevented. Differentiating adipocytes underwent a reduction in Fas expression and became resistant to FasL-induced death, with tEGF having no further survival effect. tEGF protected undifferentiated MSC from combined insults of FasL, serum deprivation, and physiologic hypoxia. Additionally, tEGF was dominant in the face of sEGF to protect MSC from FasL-induced death. Our results suggest that MSCs and differentiating osteoblasts need protective signals to survive in the inflammatory wound milieu and that tEGF can serve this function. Stem Cells2013;31:104–116