Stem cells of many different types occupy special environments within the body—so-called niches—that are important for maintaining their function. Interactions with niche components are critical for stem cells to self-renew and differentiate into multiple cell types. There is tremendous interest in understanding stem cell–niche interactions; one direction of these research efforts is the recreation of the niche in vitro.

Building a stem cell niche in vitro serves at least two purposes. First, it may permit better culture and expansion of otherwise hard-to-culture stem cells. Second, it provides researchers the opportunity to study the interaction of stem cells with their niche and to model disease states that result when these interactions are aberrant.

One relatively simple and well-used approach toward building an in vitro niche involves coculture with stromal cells or other cells found near the stem cells in vivo. Indeed, this approach continues to be used and refined for many cell types. For instance, Shinohara and colleagues recently reported that coculture with testis cells (presumed Sertoli cells) from infertile mice could support culture of mouse spermatogonial stem cells for several months (Cell Stem Cell 11, 567–578, 2012). In separate work, Shusta, Palecek and colleagues used a different coculture approach to generate organ-specific human endothelial cells. They codifferentiated human pluripotent stem cells along both the neural and endothelial lineages, thus creating an in vitro environment that mimicked the embryonic brain and functioned as a niche in which blood-brain–barrier endothelial cells could be generated (Nat. Biotechnol. 30, 783–791, 2012)

A portion of the entire light-field image of a zebrafish eye as seen before image reconstruction. Credit: Marina Corral

Fully replicating a complex and dynamic system like the stem cell niche is not trivial, however. The details will vary for different stem cell types, but the many components of a niche typically include soluble and attached signaling molecules, cell-cell interactions, cell–extracellular matrix interactions, mechanical forces in three dimensions and systemically regulated small molecules such as metabolites and oxygen.

Building a niche in vitro therefore requires not only an understanding of the biology—still incomplete for most stem cell types—but also the ability to implement the desired three-dimensional architectures, with appropriate physicochemical and biological properties (or a functional surrogate). Materials science expertise is a critical part of this endeavor. As advances in both the stem cell and the materials fields continue to accrue, they will bring a more complete reconstruction of in vitro stem cell niches within closer reach.