Mimicking cell-cell interactions at the biomaterial-cell interface for control of stem cell differentiation

The ability to regulate stem cell proliferation and differentiation has relevance in numerous medical applications, including medical devices, tissue engineering, and regenerative medicine. To control cellular behavior at the biomaterial or scaffold interface, many studies have employed surface modi...

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Bibliographic Details
Published in:Journal of biomedical materials research 2006-10, Vol.79A (1), p.94-103
Main Authors: Beckstead, Benjamin L., Santosa, Daniel M., Giachelli, Cecilia M.
Format: Article
Language:English
Subjects:
Animals
Biocompatible Materials - metabolism
biomaterials
Calcium-Binding Proteins - genetics
Calcium-Binding Proteins - metabolism
Cell Communication - physiology
Cell Differentiation - physiology
Cells, Cultured
epithelial cells
Intercellular Signaling Peptides and Proteins - genetics
Intercellular Signaling Peptides and Proteins - metabolism
Jagged-1
Jagged-1 Protein
Membrane Proteins - genetics
Membrane Proteins - metabolism
Notch
Rats
Rats, Inbred F344
Receptors, Notch - genetics
Receptors, Notch - metabolism
Serrate-Jagged Proteins
stem cells
Stem Cells - cytology
Stem Cells - physiology
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Summary:The ability to regulate stem cell proliferation and differentiation has relevance in numerous medical applications, including medical devices, tissue engineering, and regenerative medicine. To control cellular behavior at the biomaterial or scaffold interface, many studies have employed surface modifications that mimic the extracellular matrix. Strikingly absent is the immobilization of cell‐surface ligands to the biomaterial surface. One cell‐to‐cell signaling pathway that has been shown to regulate tissue development and stem cell fate is the Notch pathway. Recently, the Notch signaling pathway was identified as a key regulator of epithelial differentiation. Utilizing this knowledge, we applied an affinity immobilization scheme designed to attach and orient the Notch ligand, Jagged‐1, in an active conformation on a biomaterial surface. When epithelial stem cells were plated on the bound ligand, the Notch/CBF‐1 signaling pathway was stimulated and the cells upregulated both intermediate‐ and late‐stage differentiation markers. In addition, the ligand promoted tight clustering and extensive stratification. Soluble Jagged‐1 showed no Notch/CBF‐1 signaling and very little, if any, cell differentiating activity. The high potency of bound Jagged‐1 suggests that modification of a surface with a Notch ligand presents a powerful method to control stem cell differentiation at the cell–biomaterial interface. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res, 2006
ISSN:1549-3296
0021-9304
1552-4965
1097-4636
DOI:10.1002/jbm.a.30760