Molecular mediators of mesenchymal stem cell biology

Abstract

Mesenchymal stem cells (MSCs) have the ability to self-renew and differentiate into multiple lineages making them an appropriate candidate for stem cell therapy. In spite of achieving considerable success in preclinical models, limited success has been achieved in clinical settings with MSCs. A major impediment that is faced is low survival of MSCs in injured tissues following implantation. In order to enhance the reparative properties of MSCs, it is vital to understand the molecular signals that regulate MSC survival and self-renewal. This review assimilates information that characterizes MSCs and mentions their utilization in myocardial infarction therapy. Additionally, our attempt herein is to gather pertinent published information regarding the role of canonical Wnt and BMP signaling in regulating the potential of MSCs to self-renew, proliferate, differentiate, and survive.

Figure 2.1

Definition and molecular mediators of murine mesenchymal stem cells. Murine MSCs are CD44⁺ and SCA-1⁺, but CD45⁻and Lin⁻. As stem cells, they must give rise to self (self-renewal) and undergo trilineage differentiation toward the adipogenic, chondrogenic, and osteogenic lineages. The cascades involved in the lineage commitment are labeled with their effector molecules in parentheses.

Figure 2.2

Simplified schematic of BMP and Wnt signaling. Activation of BMP and Wnt signaling can lead to the regulation of specific target genes which affect MSC biology. Transcriptional control is exerted on the cell upon the nuclear translocation of signaling molecules: phosphorylated Smads (pSMAD 1/5/8) in the case of BMP signaling and β-catenin in the case of Wnt signaling.

Figure 2.3

Model of the role of sFRP2 in MSC self-renewal. Self-renewal is evaded by senescence, lineage commitment, and apoptosis of MSCs; Wnt and BMP signaling drive these events. sFRP2 can inhibit these cascades to indirectly drive MSC self-renewal (discontinuous line).