ABSTRACT

Since the mid-2000s, there has been increasing interest in understanding stem cell biology, particularly as it relates to the control of stem cell fate, so that cells can be engineered for therapeutic applications of tissue and organ regeneration as well as the treatment of human diseases such as heart disease, diabetes, Parkinson’s disease, and pathologies related to trauma [1-5]. However, successful cell-based treatment regimes require a more thorough understanding of what environmental signals stem cells recognize that in”uence their differentiation, how this recognition occurs, and which pathways become active as a result, in order to direct uncommitted stem cells toward a speci™c phenotype. These key environmental signals include both soluble cues as well as biochemical and biophysical stimuli presented by the extracellular matrix (ECM), a three-dimensional (3D) ™brillar protein assembly ubiquitously expressed throughout the body to which cells adhere. In this chapter, we will focus on (1) the interplay between matrix mechanics, forces, and chemistry, (2) their role in differentiating stem cells into various cell types, and (3) their application in regenerative medicine. We will also identify a few of the many open issues remaining in the ™eld. To begin such a

20.1 Introduction .......................................................................................................................... 439 20.1.1 The Types of Stem Cells ...........................................................................................440 20.1.2 The “Big Picture”: The Clinical Role Mechanobiology Should Play in Stem

Cell-Based Regenerative Medicine ........................................................................... 441 20.2 The In”uence of Physical Microenvironment on Stem Cell Differentiation ........................442