Narrow Results

Stem cells are characterized by their dual ability to self-renew and differentiate, yielding essentially unlimited numbers of progeny that can replenish tissues with either high turnover such as blood and skin or contribute to the regeneration of organs with less frequent remodeling such as muscle. In contrast to their embryonic counterparts, adult stem cells can only preserve their unique functions if they are in intimate contact with an instructive microenvironment, termed niche. Stem cells integrate a complex array of niche signals that regulate their fate, keeping them in a relatively quiescent state during homeostasis, or controlling their numbers via symmetric or asymmetric divisions in response to the regenerative demands of a tissue. This chapter provides an overview of the current state of knowledge of structural and functional hallmarks of mammalian stem cell niches and offers a perspective on how bioengineering principles could be used to deconstruct the niche and providing novel insights into the role of its specific components in the regulation of stem cell fate. Such "artificial niches" constitute powerful tools for elucidating stem cell regulatory mechanisms that should fuel the development of novel therapeutic strategies for tissue regeneration.

Cells in our tissues are exposed to complex arrays of biochemical and biophysical cues from their protein- and sugar-rich extracellular matrix (ECM). In concert with cell-intrinsic regulatory cascades, these temporally and spatially coordinated signals instruct cells to acquire specific fates, controlling, for example, cell division, differentiation, migration or apoptosis. Conversely, cells are constantly secreting signals that can trigger structural and biochemical microenvironmental changes, as is most evident during proteolytic remodeling of the ECM. The resulting reciprocal and dynamic cell-matrix interaction is crucial for tissue development, maintenance and regeneration and, if gone awry, it can be involved in disease progression such as tumor metastasis. Recent efforts in the development of synthetic biomaterials for tissue engineering aimed to mimic the cell-instructive and cell-responsive function of ECMs. This chapter focuses on the molecular design, function and application of such smart biomaterials as cell-responsive artificial ECMs that can for example actively participate in cascades of morphogenesis during tissue regeneration (see also other chapters in this book).

The following sections are included:

• Introduction
  • Adult stem cells are regulated by niches
  • Cell-cell interactions in the niche
  • Stem cell-ECM interactions in the niche
  • Stem cell interaction with soluble niche signals
  • Stem cell functions controlled by the niche

• Engineering in vitro Surrogate Models of Stem Cell Niches
  • Engineering biomaterials with niche-like physicochemical characteristics
  • Microwell arrays for high-throughput single stem cell studies
  • Niche protein microarrays
  • Dissecting cell-cell interactions in the niche in 3D
  • 3D biomolecule gradients as model niches
  • Mimicking the spatial 3D niche heterogeneity
  • From artificial niches to 3D in vitro ‘tissues’

• Conclusions and Outlook

• References