Molecular and Signaling Pathways That Modulate Mesenchymal Stem Cell Self-renewal

Abstract

Mesenchymal stem cells are multipotent stem cells that have the ability to multiply and maintain themselves while retaining the potential to differentiate into multiple lineages. This unique attribute of MSCs makes them attractive candidates for tissue repair. MSCs have been utilized in several preclinical and clinical models, but with limited progress in the translation of preclinical observations to clinical success. Inadequate survival of implanted cells in the host tissue is a substantial impediment in the progress of stem cell therapy. It is therefore a big task for the scientific community to understand and exploit the molecular signals that regulate the self-renewal and other properties that may regulate tissue engraftment of MSCs. Several published reports have examined the molecular mediators involved in MSC self-renewal and this chapter assembles the findings. Multiple developmentally conserved pathways have appeared as essential components that modulate MSC fate, including Wnt, BMP, Notch, and Hedgehog pathways. MSCs are introduced into complex microenvironments that provide competitive signals controlling self-renewal and differentiation. An understanding of the interplay between these signals provides a valuable insight into MSC regulation. Concomitantly, we have also reviewed the effects of growth factors, epigenetic modifications and telomerase activity that modulate MSC biology during self-renewal and differentiation. Particularly, we emphasize the involvement of key regulators, such as sFRP2, in maintaining MSC biology during self-renewal. This review will encompass the integration of extrinsic and intrinsic factors that determine the fate of MSCs and will highlight the major scientific developments in understanding the molecular regulators of MSC self-renewal.