Artificial extracellular matrix for embryonic stem cell cultures: a new frontier of nanobiomaterials

Abstract

Nanobiomaterials can play a central role in regenerative medicine and tissue engineering by facilitating cellular behavior and function, such as those where extracellular matrices (ECMs) direct embryonic stem (ES) cell morphogenesis, proliferation, differentiation and apoptosis. However, controlling ES cell proliferation and differentiation using matrices from natural sources is still challenging due to complex and heterogeneous culture conditions. Moreover, the systemic investigation of the regulation of self-renewal and differentiation to lineage specific cells depends on the use of defined and stress-free culture conditions. Both goals can be achieved by the development of biomaterial design targeting ECM or growth factors for ES cell culture. This targeted application will benefit from expansion of ES cells for transplantation, as well as the production of a specific differentiated cell type either by controlling the differentiation in a very specific pathway or by elimination of undesirable cell types.

Signaling of extracellular matrices for tissue regeneration and therapeutics

“…ECM: extracellular matrix, MSC: mesenchymal stem cell. [21,22]. For a better understanding, we will specifically look at the native ECM components of hard, elastic and soft tissue since all tissues can be categorized into one of them.…”

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

“…Among synthetic ECM molecules, the use of functional fusion proteins shows great promise in biology and biomedical technology due to simple and cheap production and purification strategy. Mostly three categories of synthetic ECM using recombinant fusion proteins have been explored by Akaike group in stem cell culture research (Table 1) (Nagaoka et al, 2010a;Haque et al, 2010). First, fusion proteins targeting cell-cell interacton molecules, such as cadherins (Nagaoka et al, 2006;Yue et al, 2010).…”

“…Most cell lineages, including the neuronal, mesoderm and hepatocyte lineages have been shown to be generated within the EB (Nishikawa et al, 2007). However, monitoring cell behavior and guided differentiation to specific cell lineages was not possible without the use of laborious cell sorting (Haque et al, 2010). In contrast, monolayers of freshly isolated cells or cell lines are often used as feeder cells to support EScell activities.…”

“…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). Fig.…”

The effect of recombinant E-cadherin substratum on the differentiation of endoderm-derived hepatocyte-like cells from embryonic stem cells

“…Most of the studies demonstrating hepatic differentiation from ES cells have been based on traditional culture techniques, such as embryoid body formation, aggregated colony formation on gelatin-coated plates or feeder layers. However, there are some problems with these current protocols, including spontaneous differentiation, low yield, the presence of undefined and xenogenetic compounds, necessity of cell sorting for specific lineages of cells, and considerable enzymatic stress during repeated culture [9,10]. Moreover, the cellular heterogeneity in the culture limits the diffusion of growth factors and nutrients from the culture medium and therefore, not suitable for differentiation particularly where frequent media changes are required [11,12].…”