Three‐dimensional collagen fiber remodeling by mesenchymal stem cells requires the integrin–matrix interaction

Abstract

Tissue engineering aiming to repair or regenerate damaged tissues necessitates fabricating three-dimensional biomaterial scaffolds with controlled porosity for delivering cells. To facilitate cell distribution, a strategy using stem cell-based fabrication of biomaterials was tested in type II collagen fibers. Human mesenchymal stem cells when delivered in type II collagen assembled and reorganized these matrices and differentiated into spherical chondrocytes with the synthesis of cartilage proteins. The cell-mediated assembly and reorganization of collagen fibers was not limitless and only restricted to an appropriate ratio of cell number and collagen amount. The blocking of alpha2 or beta1-integrin function with specific antibodies significantly impeded the collagen-assembly effects. In vitro chondrogenesis or in vivo cartilage formation of human mesenchymal stem cells was also dependent on the interactions between cells and surrounding matrices. This method for three-dimensional fabricating collagen fibers may generally be applied to other biomaterials, when combined with surface modification or ligand addition for cell adhesion.

Regulation of osteogenic and chondrogenic differentiation of mesenchymal stem cells in PEG-ECM hydrogels

“…Collagen and HAs are important ECM components and have been shown to induce MSC differentiation and proliferation (Chang et al 2007;Sharma et al 2007). Based on our study, the incoporation of natural ECM into PEG hydrogels can be achieved by the simple mixing of ECM and PEGDA solutions prior to the polymerization process.…”

“…However, our results show that cell spreading is minimal in these collagen-based hydrogels. This is probably attributable to the relatively low concentration of collagen in the system (0.1 mg/ml), a level that might have caused the limited osteogenic response in these hydrogels (Chang et al 2007).…”

“…Mcbeath et al (2004) have demonstrated that the adhesion of MSCs to their surrounding ECM via integrins triggers changes in cell morphology, RhoA activity, and contractile tension generated in the actin cytoskeleton, which in turn modulates a commitment switch in MSCs between the adipogenic and osteogenic lineages. Studies have demonstrated that MSCs adhere to various ECMs through integrins; however, little is known about the biological contribution of ECMs to MSC commitment and differentiation in three-dimensional (3D) culture (Chang et al 2007;Heckmann et al 2006).…”

Integrin expression and integrin-mediated adhesion in vitro of human multipotent stromal cells (MSCs) to endothelial cells from various blood vessels

“…The percent positive range for flow cytometry (FC) is from passages 2al. (2008) Delorme et al (2008) Goessler et al (2006) Majumdar et al (2000) Varas et al (2007)Chang et al (2007) …”

Bioactive Scaffolds for the Controlled Formation of Complex Skeletal Tissues

“…Collagen type-I has shown the capacity to specifically upregulate osteoblastic function and bone formation (Lynch et al, 1995), and this property has been linked to the interaction of this collagen with integrin 2 1 (M. Mizuno et al, 2000). On the other hand, collagen type-II scaffolds have shown favorable interactions for cartilage tissue engineering and cartilage regeneration, particularly in combination with GAGs (Chang et al, 2007;Wu et al, 2010). These results highlight, once again, the importance of providing the cells with scaffold compositions that mimic their natural environment.…”