Artificial Acellular Feeder Layer: An Advanced Engineered Extracellular Matrix for Stem Cell Culture

Abstract

Stem cell behavior and function is influenced by a complicated 3-D microenvironment consisting of extracellular matrix (ECM), neighboring cells, growth factors, hormones, and nutrients (Discher et al., 2009). Among them cell-ECM interaction regulates many aspects of cell behavior, including cell survival, growth, proliferation, differentiation, migration, and morphogenesis (Fig. 1) (Hynes, 1992). Tissue engineering strives to replace damaged tissues with stem cells seeded onto biologically derived or synthetic materials to mimic the regulatory characteristics of ECM and thus restore the normal control of cell function. In general, materials from natural sources (e.g., collagen, laminin or fibronectin) are advantageous for cell culture because of the presence of cell recognizable receptors (e.g., ECM molecule, galactose, can specifically recognize asialoglycoprotein receptor (ASGPR) on the hepatocytes) (Cho et al., 2006; Lutolf & Hubbell 2005). However, critical problems in biocompatibility, mechanical properties, degradation, pathogen transmission and numerous other areas remain. For tissue-engineering strategies to be successful, the complicated relationship between cells and the ECM must be simplified in a way to understand appropriate cell behavior. Through the design and expression of artificial genes using recombinant DNA technology, it is now possible to prepare artificial ECM proteins with controlled mechanical properties and with domains chosen to modulate cellular behaviour (Nagaoka et al., 2002; Ogwara et al., 2005; Azuma et al., 2010; Yue et al., 2010). This approach avoids several important limitations encountered in the use of natural ECM proteins, including complex purification, immunogenicity, heterogeneous environment, batch-to-batch (or source-to-source) variation in materials isolated from tissues, and presence of xenogenetic compounds. Moreover, the designing of artificial extracellular matrix should enable more efficient and scalable culture of embryonic stem (ES) or induced pluripotent stem (iPS) cells, as well as greater control over material properties and tissue responses (Haque et al., 2010; Nagaoka et al., 2010a).