Synthetic, Chemically Defined Polymer-Coated Microcarriers for the Expansion of Human Mesenchymal Stem Cells

Mesenchymal stem cells (MSC), also called marrow stromal cells, are adult cells that have attracted interest for their potential uses in therapeutic applications. There is a pressing need for scalable culture systems due to the large number of cells needed for clinical treatments. Here, a tailorable thin polymer coating-poly(poly(ethylene glycol) methyl ether methacrylate-ran-vinyl dimethyl azlactone-ran-glycidyl methacrylate) [P(PEGMEMA-r-VDM-r-GMA); PVG]-to the surface of commercially available polystyrene and glass microcarriers to create chemically defined surfaces for large-scale cell expansion is applied. These chemically defined microcarriers create a reproducible surface that does not rely on the adsorption of xenogenic serum proteins to mediate cell adhesion. Specifically, this coating method anchors PVG copolymer through ring opening nucleophilic attack by amine residues on poly-l-lysine that is pre-adsorbed to the surface of microcarriers. Importantly, this anchoring reaction preserves the monomer VDM reactivity for subsequent functionalization with an integrin-specific Arg-Gly-Asp peptide to enable cell adhesion and expansion via a one-step reaction in aqueous media. MSCs cultured on PVG-coated microcarriers achieve sixfold expansion-similar to the expansion achieved on PS microcarriers-and retain their ability to differentiate after harvesting.