Mimicking stem cell niches to increase stem cell expansion

Abstract

Niches regulate lineage-specific stem cell self-renewal versus differentiation in vivo and are composed of supportive cells and extracellular matrix components arranged in a three-dimensional topography of controlled stiffness in the presence of oxygen and growth factor gradients. Mimicking stem cell niches in a defined manner will facilitate production of the large numbers of stem cells needed to realize the promise of regenerative medicine and gene therapy. Progress has been made in mimicking components of the niche. Immobilizing cell-associated Notch ligands increased the self-renewal of hematopoietic (blood) stem cells. Culture on a fibrous scaffold that mimics basement membrane texture increased the expansion of hematopoietic and embryonic stem cells. Finally, researchers have created intricate patterns of cell-binding domains and complex oxygen gradients.

Figure 1. Schematic diagram illustrating several factors to consider when mimicking stem cell niches

Variations in the co-localization, clustering, surface concentration, and gradients of two immobilized ligands are represented by red spheres and blue pyramids. Matrix stiffness and topography are depicted by the rippled membrane surface. Image drawn by Mark Seniw.