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Capturing the promise of mesenchymal stem cell (MSC)-based treatments is currently limited by inefficient production of cells needed for clinical therapies. During conventional ex vivo expansion, a large portion of MSCs lose the properties that make them attractive for use in cell therapies. Decellularized extracellular matrix (dECM) has recently emerged as a promising substrate for the improved expansion of MSCs. MSCs cultured on these surfaces exhibit improved proliferation capacity, maintenance of phenotype, and increased differentiation potential. Additionally, these dECMs can be solubilized and used to coat new cell culture surfaces, imparting key biological properties of the native matrices to other surfaces such as tissue engineering scaffolds. Although this technology is still developing, there is potential for an impact in the fields of MSC biology, biomaterials, tissue engineering, and therapeutics. In this article, we review the role of dECM in MSC expansion by first detailing the decellularization methods that have been used to produce the dECM substrates; discussing the shortcomings of current decellularization methods; describing the improved MSC characteristics obtained when the cells are cultured on these surfaces; and considering the effect of the passage number, age of donor, and dECM preparation method on the quality of the dECM. Finally we describe the critical roadblocks that must be addressed before this technology can fulfil its potential, including elucidating the mechanism by which the dECMs improve the expansion of primary MSCs and the identification of a readily available source of dECM. Statement of Significance Current mesenchymal stem cell (MSC) culture methods result in premature cellular senescence or loss of differentiation potential. This creates a major bottleneck in their clinical application, as prolonged expansion is necessary to achieve clinically relevant numbers of cells. Recently, decellularized extracellular matrix (dECM) produced by primary MSC has emerged as an attractive substrate for the improved expansion of MSC; cells cultured on these surfaces retain their desired stem cell characteristics for prolonged times during culture. This review article describes the inception and development of this dECM-based technology, points out existing challenges that must be addressed, and suggests future directions of research. To our knowledge, this is the first review written on the use of dECM for improved mesenchymal stem cell expansion.

A methacrylic terpolymer system with non-fouling interfacial properties was synthesized by the random copolymerization of hexyl methacrylate, methyl methacrylate and sulfobetaine methacrylate (a monomer bearing a zwitterionic pendant group). Polymers were synthesized from feeds containing 0-15 mol.% of the zwitterion-containing methacrylate. Proton nuclear magnetic resonance verified the incorporation of sulfobetaine methacrylate into the polymer structure. Water absorption studies illustrate that the hydrophilicity of the material increases with increasing zwitterion concentration. The biological properties of the polymer were probed by fibrinogen adsorption, human umbilical vein endothelial cell adhesion and growth, and platelet adhesion. Strong resistance to protein adsorption and cell and platelet attachment was observed on materials synthesized from 15 mol.% sulfobetaine methacrylate. Results were compared to the non-fouling behavior of a PEGylated terpolymer formulation and it was observed that the poly(ethylene glycol)-containing materials were slightly more effective at resisting human umbilical vein endothelial cell adhesion and growth over a 7 day incubation period, but the zwitterion-containing materials were equally effective at resisting fibrinogen adsorption and platelet adhesion. The zwitterion-containing materials were electrospun into three-dimensional random fiber scaffolds. Materials synthesized from 15 mol.% of the zwitterion-containing monomer retained their non-fouling character after fabrication into scaffolds.