Mesenchymal stem cell (MSC)-based treatments have shown promise for improving tendon healing and repair. MSCs have the potential to differentiate into multiple lineages in response to select chemical and physical stimuli, including into tenocytes. Cell elongation and cytoskeletal tension have been shown to be instrumental to the process of MSC differentiation. Previous studies have shown that inhibition of stress fiber formation leads MSCs to default toward an adipogenic lineage, which suggests that stress fibers are required for MSCs to sense the environmental factors that can induce differentiation into tenocytes. As the Rho/ROCK signal transduction pathway plays a critical role in both stress fiber formation and in cell sensation, we examined whether the activation of this pathway was required when inducing MSC tendon differentiation using rope-like silk scaffolds. To accomplish this, we employed a loss-of-function approach by knocking out ROCK, actin and myosin (two other components of the pathway) using the specific inhibitors Y-27632, Latrunculin A and blebbistatin, respectively. We demonstrated that independently disrupting the cytoskeleton and the Rho/ROCK pathway abolished the expression of tendon differentiation markers and led to a loss of spindle morphology. Together, these studies suggest that the tension that is generated by MSC elongation is essential for MSC teno-differentiation and that the Rho/ROCK pathway is a critical mediator of tendon differentiation on rope-like silk scaffolds.
The aging hand is characterized by skin changes and soft-tissue deflation, which leads to rhytides, dermal atrophy, and distinct anatomical structures. Soft-tissue deflation and prominent hand anatomy can be corrected with volume augmentation using dermal fillers or lipofilling. Fat transfer volumizes the hand with prolonged durability and efficacy, autologous tissue replacement, and possible dermal regeneration. The senior author's (R.J.R.) technique for hand rejuvenation is described, which uses minimal access and blunt dissection to effectively augment the soft-tissue compartments of the hand. This approach addresses the prominent aged anatomy of the hand, providing excellent contour and aesthetic outcomes.
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