Effects of Immobilized Glycosaminoglycans on the Proliferation and Differentiation of Mesenchymal Stem Cells

Abstract

Mesenchymal stem cells (MSCs) are adult stem cells with potential for multilineage differentiation. They represent an attractive cell source alternative to embryonic stem cells for therapeutic applications. Optimal utilization of MSCs for tissue engineering requires improved biomaterials that can enhance their growth and direct differentiation. The biological activity of glycosaminoglycans (GAGs) has been previously exploited for use in tissue engineering applications. In this study, MSC proliferation and differentiation was studied on GAG-derivatized chitosan membranes. The GAGs included heparin, heparan sulfate, dermatan sulfate, chondroitin 4-sulfate, chondroitin 6-sulfate, and hyaluronic acid. The covalent GAG immobilization method and amount of immobilized GAG were varied. It was found that MSC growth increased as much as fivefold on GAG-immobilized surfaces compared to tissue culture plastic and chitosan-only controls. The MSC growth rates increased significantly with increasing GAG density on the culture surfaces. The MSC proliferation rates on heparin, heparan sulfate, dermatan sulfate, and chondroitin 6-sulfate exhibited nonlinear increases with the level of fibronectin binding on these surfaces. In contrast, MSC proliferation on hyaluronic acid and chondroitin 4-sulfate was found to be independent of fibronectin or vitronectin binding on the surfaces, suggesting that these GAGs influenced MSC proliferation through different mechanisms. In conclusion, the results indicate that GAG immobilization on chitosan scaffolds provides an effective means of manipulating MSC proliferation and has promising potential for directing MSC differentiation in tissue engineering applications employing chitosan.

Sulfation patterns of exogenous chondroitin sulfate affect chondrogenic differentiation of ATDC5 cells

“…Many studies have been conducted with the aim of developing effective scaffolds [2]. Moreover, various molecules have been applied to scaffolds to try to modify them and create a suitable microenvironment in which cells can differentiate properly and maintain chondrogenic properties [3]. There have been some successful modifications with glycosaminoglycans (GAGs), such as hyaluronan, heparan sulfate, or chondroitin sulfate (CS) [3].…”

“…Moreover, various molecules have been applied to scaffolds to try to modify them and create a suitable microenvironment in which cells can differentiate properly and maintain chondrogenic properties [3]. There have been some successful modifications with glycosaminoglycans (GAGs), such as hyaluronan, heparan sulfate, or chondroitin sulfate (CS) [3]. Of these GAGs, CS, a major component of extracellular matrices (ECMs) in cartilage tissue, is a favored candidate biomaterial for an effective scaffold modifier [4][5][6].…”

Cell-Biomaterial Interactions Reproducing a Niche

“…Therefore a biofunctionalization of a scaffold surface should not focus on the presentation of a uniform coating to engage a single receptor, but rather identify the properties that control the presentation of integrin-specific epitopes within the coatings (Keselowsky, Collard et al 2005). Clearly several additional chemical modifications can be introduced and applied to almost any specific substrata, provided that the proper chemistry is used; indeed many strategies and approaches are currently being tested (Fu, Wang et al 2011), ranging from simple coatings onto specific substrates (Uygun, Stojsih et al 2009), to the contemporary use of genetic engineering and structural approaches (Benoit, Schwartz et al 2008;Gorsline, Tangkawattana et al 2010), to combinations of matrix-mimicking ligands and engineered structured nanomatrices (Anderson, Kushwaha et al 2009). The same natural extracellular matrix is per se able to induce specific cell commitment (Chen, Dusevich et al 2007).…”

Advances in Regenerative Medicine

“…Therefore a biofunctionalization of a scaffold surface should not focus on the presentation of a uniform coating to engage a single receptor, but rather identify the properties that control the presentation of integrin-specific epitopes within the coatings (Keselowsky, Collard et al 2005). Clearly several additional chemical modifications can be introduced and applied to almost any specific substrata, provided that the proper chemistry is used; indeed many strategies and approaches are currently being tested (Fu, Wang et al 2011), ranging from simple coatings onto specific substrates (Uygun, Stojsih et al 2009), to the contemporary use of genetic engineering and structural approaches (Benoit, Schwartz et al 2008;Gorsline, Tangkawattana et al 2010), to combinations of matrix-mimicking ligands and engineered structured nanomatrices (Anderson, Kushwaha et al 2009). The same natural extracellular matrix is per se able to induce specific cell commitment (Chen, Dusevich et al 2007).…”