Fibronectin, Vitronectin, and Collagen I Induce Chemotaxis and Haptotaxis of Human and Rabbit Mesenchymal Stem Cells in a Standardized Transmembrane Assay

Abstract

The mesenchymal stem cell (MSC) is a critical element in tissue repair and regeneration. Its ability to differentiate into multiple connective tissue cell types and to self-renew has made it a prime candidate in regenerative medicine strategies. Currently, the environmental cues responsible for in situ recruitment and control of MSC distribution at repair sites are not entirely revealed and in particular the role of extracellular matrix (ECM) proteins as motogenic factors has not been studied. Here we have used a standardized transmembrane chemotaxis assay to assess the chemotactic and haptotactic potential of fibronectin, vitronectin, and collagen type 1 on MSCs from both rabbit and human origin. The use of both cell types was based in part on the widespread use of rabbit models for musculoskeletal-related tissue engineering and repair models and their unknown correspondence to human in terms of MSC migration. The optimized assay yielded a greatly increased chemotactic response toward known factors such as platelet-derived growth factor-BB (PDGF)-BB compared to previous studies. Our primary finding was that all three ECM proteins tested (fibronectin, vitronectin, and collagen I) induced significant motogenic activity, in both soluble and insoluble forms, for both rabbit and human MSCs. These results suggest that ECM proteins could play roles as significant as cytokines in the recruitment of pluripotential repair cells wound and tissue repair sites. Furthermore, designed ECM coatings of scaffolds or implants could provide a new tool to control both cell influx and outflux from the scaffold post-implantation. Finally, the similarity of motogenic behavior of both rabbit and human cells suggests the rabbit is a reliable model for assessing MSC recruitment in repair and regeneration strategies. 489

Tendon-Derived Extracellular Matrix Enhances Transforming Growth Factor-β3-Induced Tenogenic Differentiation of Human Adipose-Derived Stem Cells

“…Color images available online at www.liebertpub.com/tea noncollagenous proteins, including fibronectin, fibromodulin, biglycan, and decorin, all of which are known to regulate MSC activities, such as adhesion, proliferation, stemness, and differentiation. 21,[43][44][45] In addition, a variety of growth factors, such as TGF-b, IGF-1, vascular endothelial growth factor (VEGF), and connective tissue growth factor (CTGF), were found embedded in the decellularized tECM. 46 How these bioactive molecules, along with other yet-to-be-identified components in the tECM, contribute to the bioactivity of the tECM in our results remains to be investigated.…”

Cell adhesion and response to synthetic nanopatterned environments by steering receptor clustering and spatial location

“…The functional role of ECM gradients still remains to be elucidated, though their role in guiding the migration of mesenchymal stem cells appears to be crucial during tissue repair or regeneration. For example, fibronectin, collagen I and vitronectin, presented in both soluble and bound gradient, are able to induce cell motility (Thibault et al, 2007). Also proteoglycans play a role in the spatial and temporal control of cell movement imposing directionality and stop-go choice of migrating cells (Cattaruzza and Perris, 2005).…”

Low levels of TGF-β1 enhance human umbilical cord-derived mesenchymal stem cell fibronectin production and extend survival time in a rat model of lipopolysaccharide-induced acute lung injury

“…Furthermore, chemotaxis and homing of MSCs are closely associated with ECM components. A previous study demonstrated that three ECM proteins, fibronectin (FN), vitronectin and collagen I (Col-I), induce significant mitogenic activity in MSCs (17). The ECM also stimulates neuronal differentiation of MSCs and serves as a nerve-regenerative scaffold (18,19).…”