Soluble Factors on Stage to Direct Mesenchymal Stem Cells Fate

Cristina Sobacchi, Eleonora Palagano, Anna Villa, Ciro Menale, Cristina Sobacchi, Eleonora Palagano, Anna Villa, Ciro Menale

Abstract

Mesenchymal stem cells (MSCs) are multipotent stromal cells that are identified by in vitro plastic adherence, colony-forming capacity, expression of a panel of surface molecules, and ability to differentiate at least toward osteogenic, adipogenic, and chondrogenic lineages. They also produce trophic factors with immunomodulatory, proangiogenic, and antiapoptotic functions influencing the behavior of neighboring cells. On the other hand, a reciprocal regulation takes place; in fact, MSCs can be isolated from several tissues, and depending on the original microenvironment and the range of stimuli received from there, they can display differences in their essential characteristics. Here, we focus mainly on the bone tissue and how soluble factors, such as growth factors, cytokines, and hormones, present in this microenvironment can orchestrate bone marrow-derived MSCs fate. We also briefly describe the alteration of MSCs behavior in pathological settings such as hematological cancer, bone metastasis, and bone marrow failure syndromes. Overall, the possibility to modulate MSCs plasticity makes them an attractive tool for diverse applications of tissue regeneration in cell therapy. Therefore, the comprehensive understanding of the microenvironment characteristics and components better suited to obtain a specific MSCs response can be extremely useful for clinical use.

Keywords: RANKL; bone marrow microenvironment; cytokines; growth factors; hormones; mesenchymal stem cells.

Figures

Figure 1
Figure 1
Molecular pathways activated by soluble factors influencing bone marrow mesenchymal stem cells (MSCs) differentiation. Simplified representation of cellular players in bone marrow microenviroment (BM-ME) showing that growth factors, hormones, and cytokines, by binding to their respective receptors on the MSC plasma membrane, trigger activation of signaling cascades that ultimately result in gene expression regulation relevant for MSCs differentiation fate.
Figure 2
Figure 2
Effects of soluble factors on bone marrow mesenchymal stem cells (MSCs) trilineage differentiation. Schematic representation of the effect exerted by the described soluble molecules on MSCs osteogenic, chondrogenic, and adipogenic differentiation. Green circle, enhancement; red circle, suppression; orange circle, context-dependent regulation; TBD, to be determined.

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