Elongated cell morphology and uniaxial mechanical stretch contribute to physical attributes of niche environment for MSC tenogenic differentiation.

Specific lineage differentiation of mesenchymal stem cells (MSCs), such as osteogenic and chondrogenic differentiation, is the major subject of MSC-based musculoskeletal tissue regeneration. Nevertheless, an ideal induction regime for MSC tenogenic differentiation is less explored. While induced differentiation of MSCs using chemical signalling, such as growth factors, has been the mainstream methodology in the past decades, recent studies show that a physical signal is one of the major attributes that composes in vivo niches of MSCs, and is a potent factor in determining MSC fate in several in vitro models; for example, control of cell shape with surface topography can drive MSCs towards a specific lineage differentiation. Mechanical signals also play important roles in the differentiation of MSCs towards certain lineages. Tendon is a connective tissue which is subjected to dynamic uniaxial mechanical stretch by physical activity. Additionally, tenocytes have a unique elongated cell morphology and are aligned in parallel with collagen fibres. We thus would hypothesize that both enforced elongated cell morphology and uniaxial mechanical stretch signal contribute to the major physical niche attributes of tenocytes' in vivo microenvironment, and mimicking these physical signals may be sufficient to induce tenogenic differentiation of MSCs.