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 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.
Beckstead
Benjamin L
BL
Department of Bioengineering, University of Washington, Seattle, Washington 98195, USA.
Santosa
Daniel M
DM
Giachelli
Cecilia M
CM
D000818:Animals; D001672:Biocompatible Materials / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism; D002450:Cell Communication / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D000072100:Jagged-1 Protein; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D051880:Receptors, Notch / Q000235:genetics / Q000378:metabolism; D000072099:Serrate-Jagged Proteins; D013234:Stem Cells / Q000166:cytology / Q000502:physiology*
D001672:Biocompatible Materials; D002135:Calcium-Binding Proteins; D036341:Intercellular Signaling Peptides and Proteins; C000606275:Jag1 protein, rat; D000072100:Jagged-1 Protein; D008565:Membrane Proteins; D051880:Receptors, Notch; D000072099:Serrate-Jagged Proteins