Engineering a stem cell house into a home

Stem cells, in contrast to progenitor cells, harbor the unique ability to divide and generate additional stem cells (selfrenew) and to produce progeny that differentiate into tissue-specific cells with defined physiological functions. These properties make embryonic stem (ES) cells, induced pluripotent stem (iPS) cells [1,2] and tissue-specific adult stem cells (aSCs) well suited for regenerative medicine applications. Nevertheless, the clinical use of ES cells, iPS cells, and aSCs for cell-based therapies is hindered by a number of critical hurdles. In addition to the ethical considerations associated with the generation of ES cells, cell populations derived from totipotent ES and iPS cells have the potential to generate teratomas upon transplantation if the fidelity and efficiency of differentiation and enrichment protocols are not ideal. aSCs are intrinsically wired to differentiate efficiently into cells from their tissue of origin. However, their relative infrequency in tissues and our limited understanding of the parameters regulating their differentiation and self-renewal currently precludes most aSC-based clinical applications. However, the medical potential of stem cells, specifically aSCs, can be realized by placing unprecedented emphasis on elucidating the mechanisms governing their behavior and fate.aSC regulation is largely attributed to dynamic bidirectional interactions made with the tissue environment in the immediate vicinity of the cell, termed the 'niche' (Figure 1). First formally described in the fruit fly, Drosophila [3,4], the stem cell niche, or microenvironment, is composed of both biochemical (growth factors, cytokines, receptor ligands, and so on) and biophysical (matrix stiffness, topography/architecture, fluidity, and so on) factors that act singly and in concert to continuously modulate cell fate. Despite widespread recognition of its importance, our understanding of niche elements and their cell and molecular influence on aSCs is limit