Maintenance and culture of MSCs

The phenotype and behavior of mesenchymal stem cells (MSCs) are regulated by cues from the extracellular environment. At present, the methods by which MSCs are isolated from tissue sources and commonly expanded ex vivo can decrease their number and render them functionally ineffective for transplantation and tissue regeneration. For this reason, MSCs used in both research and clinical applications should be maintained in culture conditions that replicate their native, tissue-specific microenvironments (niches) in vivo. Until recently, researchers have expended significant amounts of time and energy in developing a variety of models to untangle the relationship between MSC behavior and the unique combination of biochemical, architectural, and mechanical cues contained in the native stem cell niche. However, most of these approaches result in overly simplistic and artificial models that minimize the inherent complexity of the extracellular environment and provide information/data that are difficult to translate. In this chapter, we will describe a novel culture system, based on decellularized, stromal cell-derived extracellular matrix (ECM), which provides a physiologically relevant surrogate for the native stem cell niche and a sophisticated ex vivo environment for studying stem cell behavior, modeling age-related pathologies, and potentially controlling cell-fate for therapeutic applications.