Differentiation stage alters matrix control of stem cells

Abstract

Cues from the material to which a cell is adherent (e.g., adhesion ligand presentation, substrate elastic modulus) clearly influence the phenotype of differentiated cells. However, it is currently unclear if stem cells respond similarly to these cues. This study examined how the overall density and nanoscale organization of a model cell adhesion ligand (arginine-glycine-aspartic acid [RGD] containing peptide) presented from hydrogels of varying stiffness regulated the proliferation of a clonally derived stem cell line (D1 cells) and preosteoblasts (MC3T3-E1). While the growth rate of MC3T3-E1 preosteoblasts was responsive to nanoscale RGD ligand organization and substrate stiffness, the D1 stem cells were less sensitive to these cues in their uncommitted state. However, once the D1 cells were differentiated towards the osteoblast lineage, they became more responsive to these signals. These results demonstrate that the cell response to material cues is dependent on the stage of cell commitment or differentiation, and these findings will likely impact the design of biomaterials for tissue regeneration.

Controlling Stem Cell Fate with Material Design

“…A clonally derived bone marrow stem cell line (D1), able to differentiate to adipo-, chondro-, and osteogenic lineages, and a more committed pre-osteoblast cell line were cultured in the presence of RGD-coupled alginate gels with varied mechanics (20,60,110 kPa) by changing the amount of Ca 2þ . [146] The pre-osteoblasts showed higher mechanosensitivity (as evidenced by cell proliferation) than the undifferentiated D1 cell line. However, when the D1 cells were pre-differentiated to a pre-osteoblast-like state, their mechanosensitivity increased dramatically and was nearly identical to the MC3T3 cells.…”

Evaluation of Multifunctional Polysaccharide Hydrogels with Varying Stiffness for Bone Tissue Engineering

“…74 Organization, motility, and supplement-induced differentiation of MC3T3-E1 osteoblasts cultured on collagen-modified polyacrylamide gels and arginine-glycine-aspartate (RGD)-modified PEG hydrogels (2D) were influenced by matrix stiffness. 75,76 Therefore, it is important to design gels of optimal stiffness that can promote growth and proliferation of these different cell types. 77 Since these hydrogels are proposed for bone formation in maxillofacial and dental bone defects, there is a high chance of antimicrobial contamination in those sites.…”

The Interplay Between Cell Adhesion Cues and Curvature of Cell Adherent Alginate Microgels in Multipotent Stem Cell Culture

“…20 The quantitative relationship between the RGD peptide density of a microgel and cellular activities agreed well with studies conducted using cells adhered to hydrogel discs with diameters of centimeter scale. 25,28 Further, unlike the cell adhesion hydrogels with dimensions of the centimeter scale, the use of hydrogel substrates with diameters of the micrometer to millimeter scales demonstrated the role the cell adhesion substrate curvature has on cellular activities. It is well known that shear stress controlled with flow rates regulates diverse cellular activities,…”