Extracellular matrix-induced signaling pathways in mesenchymal stem/stromal cells

Abstract

The extracellular matrix (ECM) is a crucial component of the stem cell microenvironment, or stem-cell niches, and contributes to the regulation of cell behavior and fate. Accumulating evidence indicates that different types of stem cells possess a large variety of molecules responsible for interactions with the ECM, mediating specific epigenetic rearrangements and corresponding changes in transcriptome profile. Signals from the ECM are crucial at all stages of ontogenesis, including embryonic and postnatal development, as well as tissue renewal and repair. The ECM could regulate stem cell transition from a quiescent state to readiness to perceive the signals of differentiation induction (competence) and the transition between different stages of differentiation (commitment). Currently, to unveil the complex networks of cellular signaling from the ECM, multiple approaches including screening methods, the analysis of the cell matrixome, and the creation of predictive networks of protein–protein interactions based on experimental data are used. In this review, we consider the existing evidence regarded the contribution of ECM-induced intracellular signaling pathways into the regulation of stem cell differentiation focusing on mesenchymal stem/stromal cells (MSCs) as well-studied type of postnatal stem cells totally depended on signals from ECM. Furthermore, we propose a system biology-based approach for the prediction of ECM-mediated signal transduction pathways in target cells.

Tendon-associated gene expression precedes osteogenesis in mid-palatal suture establishment

“…Cell differentiation is guided by several signaling networks, including WNT, BMP, TGFs, Hh, and FGF pathways. Development and maintenance of the heterogeneous components in the developing palate such as mineralizing bone, vasculature, nerves, epithelium, and cartilage likely not only involves coordinated signaling for lineage differentiation (Chen et al, 2021; Han et al, 2018; Novoseletskaya et al, 2023; Picoli et al, 2024; Tower et al, 2021), but must also include mechanosensitive elements. Thus, it is important to consider how changes in the mechanical environment following surgical intervention might alter the growth potential of the target tissue.…”

Integration of Electrospun Scaffolds and Biological Polymers for Enhancing the Delivery and Efficacy of Mesenchymal Stem/Stromal Cell Therapies

“…Multiple integrins are abundantly found on the surface of many stem cell types. Subunit β1 is often linked to the stem cell phenotype as it aids in homing to the niche, maintaining stemness, and promoting proliferation [15]. In the case of MSCs, it has been shown that the interaction of human bone-marrow-derived MSCs (BMSCs) with type I collagen through α2β1 and α11β1 integrins promotes survival and proliferation [15,16].…”

“…Subunit β1 is often linked to the stem cell phenotype as it aids in homing to the niche, maintaining stemness, and promoting proliferation [15]. In the case of MSCs, it has been shown that the interaction of human bone-marrow-derived MSCs (BMSCs) with type I collagen through α2β1 and α11β1 integrins promotes survival and proliferation [15,16]. Aside from integrins, MSCs have also been shown to interact with ECM components through discoidin domain receptors, CD44, syndecans, and mechanosensitive ion channels [15].…”

“…In the case of MSCs, it has been shown that the interaction of human bone-marrow-derived MSCs (BMSCs) with type I collagen through α2β1 and α11β1 integrins promotes survival and proliferation [15,16]. Aside from integrins, MSCs have also been shown to interact with ECM components through discoidin domain receptors, CD44, syndecans, and mechanosensitive ion channels [15]. These receptors interact with a wide variety of biological polymers in the ECM, which is composed of a variety of fibers and ground substance (i.e., glycoproteins, proteoglycans, and glycosaminoglycans [GAGs]).…”

Dynamic extracellular proximal interaction profiling reveals Low-Density Lipoprotein Receptor as a new Epidermal Growth Factor signaling pathway component

“…These components are vital for cells to interface with their milieu, transmitting extracellular signals intracellularly. The dynamic and fluid nature of the plasma membrane allows cells to adapt to environmental changes ( 2 ) by interacting with the extracellular matrix ( 3 , 4 ), ligands ( 5 ) (e.g., cytokines and growth hormones), and neighboring cells (6). These interaction events are crucial in regulating signaling and driving cellular processes such as survival, proliferation, migration, or apoptosis ( 1 ).…”