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FIGURE 1 Schematic of the stem cell niche. Soluble small molecules, soluble and immobilized growth factor and morphogen proteins, extracellular matrix components, and intercellular components collaborate to regulate stem cell behavior. In addition, numerous physical and engineering principles modulate the manner in which these components present information, including mechanical properties, spatial organization and temporal variation in the presentation of cues, topographical features of the niche on the nano-and microscale, mass transport properties, and electrostatics.

cal roles in regulating stem cell function. However, biology encodes regulatory information to cells not only in the binary absence or presence of a given molecule but also in numerous biophysical aspects of tissues—mechanics, topographical features, electrostatics, biological transport phenomena, and spatiotemporal variation in each of these cues (Figure 1). Thus a major difficulty in studying and manipulating the biophysical properties of the niche is that they are not monogenic but depend on the properties of many molecules and genes.

An emerging theme in stem cell research is to use engineered systems in cell culture—ranging from synthetic materials to microfluidic devices—to systematically vary these biophysical properties and thereby study their effects on stem cells, that is, to provide an “x-axis” in a manner that is not currently possible with genetic approaches. While there are inherent challenges with this paradigm—including establishing the in vivo relevance of findings, as well as integrating engineering and biology approaches to explore the underlying mechanisms—these engineering studies have broadened the field’s view of the stem cell niche (Discher et al. 2009; Keung et al. 2010). Furthermore, because of the complexity of their endogenous niches, stem cells are exceedingly difficult to control in culture; therefore, each biophysical property offers a new opportunity to engineer synthetic systems and materials to control stem cell function for regenerative medicine applications.

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