The Roles of Insulin-Like Growth Factors in Mesenchymal Stem Cell Niche

Figure 1

Stem cell niche in vivo. The stem cell niche is a complex compartment surrounding mesenchymal stem cells (MSCs) directing their identity preservation via cellular and acellular components. Various clues and signals are exchanged between MSCs, stromal cells, and progenitor cells and the extracellular matrix containing different soluble factors, oxygen tension, and pH. Therefore, MSC niche manipulates the stemness state of MSCs following growth and regeneration demand. IGFs can signal via paracrine/autocrine (produced locally by the tissue) or endocrine (delivered by blood supply) routes to interact with IGF-1 receptor, IGF-2 receptor, or the insulin receptor on MSCs and other cells. IGFBPs (extracellular and/or intracellular actions) can modify IGF actions and affect their stability and degradation. Other receptors and integrins are expressed in MSCs and can be affected by extracellular microenvironment. MSC differentiation occurs by signal transduction which controls the shutdown of pluripotency-associated genes, such as OCT4, SOX2, and NANOG, for the upregulation of differentiation genes. For example, MSCs can give rise to all mesodermal lineages depending on the transcription factor expressed to generate adipose, cartilage, bone, and muscle. Also, transdifferentiation of MSCs into endodermal and ectodermal lineages can occur, as reported by in vitro studies.