Advances in the Combined Use of Adult Cell Therapy and Scaffolds for Brain Tissue Engineering
Relatively little is known about the cellular and molecular mechanisms underlying the control of mesenchymal stem cell (MSC) proliferation, differentiation, and survival. This presents difficulties in following and characterizing cells along the lineage because of our inability to isolate and obtain a sufficient number of homogeneous MSCs using current culture systems for in vitro expansion. Adjusting the cellular machinery to allow greater proliferation can lead to other unwanted outcomes, such as unmanageable precancerous changes, or differentiation down an undesired pathway. Recently, it has become increasingly evident that the extracellular matrix (ECM) is an important component of the cellular niche in a tissue, supplying critical biochemical and physical signals to initiate and sustain cellular functions. Indeed, it is very doubtful that the intricate and highly ordered nature of the ECM could be reproduced with synthetic or purified components. This review cites evidence that supports an alternative approach for maintenance of MSCs by simulating in vitro the bone marrow ECM, where MSCs reside in vivo, and discusses the potential mechanisms whereby the ECM regulates the exposure of cells to growth factors that subsequently control MSC replication and differentiation, and also how the ECM provides unique cues that govern the lineage specification and differentiation of MSCs.