Microenvironmental control of stem cell fate

Abstract

The field of regenerative medicine has witnessed impressive advances over the past 25–30 years, moving us ever closer to the goal of translating engineered tissue constructs into human patients. However, despite an exponentially expanding literature documenting advances in biomaterials and stem cell biology, generating tissues that function equivalently to the native tissues they are intended to replace remains an enormous challenge. Translating stem cell-based therapies from the bench to the bedside requires a better understanding of the mechanisms by which stem cell fate decisions are controlled. Extrinsic factors in the cellular microenvironment, particularly the extracellular matrix (ECM), include chemical, mechanical, and topographic cues, which in turn alter cell adhesion, cell shape, and cell migration, and activate signal transduction pathways to influence gene expression, proliferation, and differentiation. This chapter focuses on the links between the ECM microenvironment and the control of cell fate. The concept of the stem cell niche is also highlighted, along with evidence that the proximity of stem cells to the microvasculature may be instructive. Finally, the impact of these findings for the design and clinical utility of biomaterials for cardiac regenerative medicine is discussed.