2 - Stem cell culture: mimicking the stem cell niche in vitro

Abstract

Stem cells have been defined as unspecialized cells with unique properties such as the capacity for prolonged proliferation without loss of potential, and the ability to differentiate into specialized cell types. They have potential in the design of cellular therapies for degenerative diseases and can be used as models for pharmacological and developmental biology research. However, before their enormous potential can be realized, it is crucial to fully understand the cellular and molecular mechanisms governing their self-renewal and differentiation. One of the major objectives in this field is to study the regulation of stem cell function in vivo in tissues where these cells reside – in the endogenous ‘stem cell niche’. The principle behind this, proposed 30 years ago, is that tissues house stem cells within specific locales and stem cell fate is influenced by interactions with several components of their three-dimensional microenvironment, including soluble and immobilized factors, the extracellular matrix (ECM) and signals presented by neighboring cells. It is recognized that this microenvironment presents specific biomechanical signals that strongly influence stem cell behavior. They are often represented as static microenvironments, but stem cell niches are spatially and temporally dynamic, integrating long-term signals with short-term and injury-mediated responses. Thus, the successful application of stem cells depends on a capacity to recreate this complex and dynamic in vivo microenvironment. Studies on stem cell niches in invertebrates and mammals have begun to unravel the regulatory mechanisms involved in these complex cellular interactions, and have inspired stem cell bioengineers to develop biomaterials and technologies that recreate biochemical and structural aspects of in vivo microenvironments as well as microfabricated structures that allow precise control of key niche parameters. These culture platforms are useful for studying stem cell function at a single-cell level and in a high-throughput manner.