Lineage Commitment, Signaling Pathways, and the Cytoskeleton Systems in Mesenchymal Stem Cells

Abstract

Mesenchymal stem cells (MSCs) from adult tissues are promising candidates for personalized cell therapy and tissue engineering. Significant progress was achieved in our understanding of the regulation of MSCs proliferation and differentiation by different cues during the past years. Proliferation and differentiation of MSCs are sensitive to the extracellular matrix (ECM) properties, physical cues, and chemical signaling. Sheath stress, matrix stiffness, surface adhesiveness, and micro-and nanotopography define cell shape and dictate lineage commitment of MSCs even in the absence of specific chemical signals. We discuss mechanotransduction as the major route from ECM through the cytoskeleton toward signaling pathways and gene expression. All components of the cytoskeleton from primary cilium and focal adhesions (FAs) to actin, microtubules (MTs), and intermediate filaments (IFs) are involved in the mechanotransduction. Differentiation of MSCs is regulated via the complex network of interrelated signaling pathways, including RhoA/ROCK, Akt/Erk, and YAP/TAZ effectors of Hippo pathway. These pathways could be regulated both by chemical and mechanical stimuli. Attenuation of these pathways in MSCs results in specific changes in FAs and actin cytoskeleton. Besides, differentiation of MSCs affects MTs and IFs. Recent findings highlight the role of intranuclear actin in the regulation of transcription factors in response to mechanical environmental stimuli. Alterations of cytoskeletal components reflect the MSC senescence state and their migratory capacity. In this review, we discuss the relationships between the molecular interactions in signaling pathways and morphological response of cytoskeletal components and reveal the complex interrelations between cytoskeleton systems and signaling pathways during lineage commitment of MSCs.

Timely Supplementation of Hydrogels Containing Sulfated or Unsulfated Chondroitin and Hyaluronic Acid Affects Mesenchymal Stromal Cells Commitment Toward Chondrogenic Differentiation

“…The stemness (stem cell properties), cell commitment and differentiation of MSCs are regulated by ECM and physical and chemical cues. Changes in ECM composition may affect MSC biological functions by either promoting lineage selection and/or differentiation or maintaining undifferentiated status (Saidova and Vorobjev, 2020). In this context, we decided to evaluate the role of HA, CS and beyond BC in cell commitment and chondrocyte differentiation of MSCs by using the experimental approach depicted in Figure 1.…”

Bone physiological microenvironment and healing mechanism: Basis for future bone-tissue engineering scaffolds

“…Changes in the cytoskeletal system can activate RhoA-ROCK, Akt/Erk, and YAP/TAZ effectors of the Hippo pathway, which will further affect the stem cell fate ( Fig. 5 b) [ 230 , 231 ].…”

Characterization of Mesenchymal Stem Cell Differentiation within Miniaturized 3D Scaffolds through Advanced Microscopy Techniques

“…In this study an investigation of the effect of Nichoids on MSCs during long-term differentiation was performed by optical techniques comparing fluorescence microscopy with label-free and vital nonlinear optical microscopy. Adipogenesis and chondrogenesis of MSCs were considered since tissue characteristics are slightly different in stiffness and genesis [36] and several protocols for in vitro differentiation are available and easy to replicate [30,37]. First, a qualitative observation of MSCs morphology and spatial configuration (Figure 1), combined with a quantitative study of their nuclear shape via confocal fluorescence inspections ( Figure 2) was performed in order to assess if evident cellular remodeling arose in cells exposed to chemical differentiation factors with respect to cells exposed to basal growth media inside Nichoids.…”