Regulation of mesenchymal stem cell differentiation by key cell signaling pathways

Mesenchymal stem cells (MSCs) are multipotent stem cells that have the ability to differentiate into osteocytes, chondrocytes, adipocytes, myoblasts, fibroblasts, and neuronal stem cells. MSCs are primarily derived from the bone marrow, adipose tissue, umbilical cord, and other sources such as menstrual blood and endometrium, peripheral blood, amniotic fluid, and dental pulp. MSCs are one of the most appealing choices in regenerative medicine for the development of numerous therapeutic applications due to their low immunogenicity and immunomodulatory function. Along with this, MSCs have an inherent ability to self-renew and undergo multilineage differentiation. Studies have revealed the various factors that influence the transdifferentiation of MSCs, and various signaling pathways that have been found to be involved in particular lineage commitments. MSC transdifferentiation is regulated by factors such as bone morphogenic protein (BMPs), TGF-β family proteins, RANKL, and signaling pathways such as Wnt/β-catenin signaling pathway, TGF-β/SMAD (suppressor of mothers against decapentaplegic) signaling pathway, Notch signaling pathway, Sonic Hedgehog signaling pathway, platelet-derived growth factor signaling pathway, FGF signaling pathway, JAK/STAT signaling pathway, and NELL-1 signaling pathway. Epigenetic mechanisms such as histone alteration, DNA methylation, and acetylation play a crucial role in the development of MSCs and also in their differentiation into specific lineages.