Engineered Microenvironments for Controlled Stem Cell Differentiation

In a developing organism, tissues emerge from coordinated sequences of cell renewal, differentiation, and assembly that are orchestrated by spatial and temporal gradients of multiple regulatory factors. The composition, architecture, signaling, and biomechanics of the cellular microenvironment act in concert to provide the necessary cues regulating cell function in the developing and adult organism. With recent major advances in stem cell biology, tissue engineering is becoming increasingly oriented toward biologically inspired in vitro cellular microenvironments designed to guide stem cell growth, differentiation, and functional assembly. The premise is that to unlock the full potential of stem cells, at least some aspects of the dynamic three-dimensional (3D) environments that are associated with their renewal, differentiation, and assembly in native tissues need to be reconstructed. In the general context of tissue engineering, we discuss the environments for guiding stem cell function by an interactive use of biomaterial scaffolds and bioreactors, and focus on the interplay between molecular and physical regulatory factors. We highlight some illustrative examples of controllable cell environments developed through the interaction of stem cell biology and tissue engineering at multiple levels.