Abstract
Support of somatic growth is a fundamental requirement of tissue-engineered valves. However, efforts thus far have been unable to maintain this support long term. A key event that will determine the valve's long-term success is the extent to which healthy host tissue remodeling can occur on the valve soon after implantation. The construct's phenotypic-status plays a critical role in accelerating tissue remodeling and engineered valve integration with the host via chemotaxis. In the current study, human bone-marrow-derived mesenchymal stem cells were utilized to seed synthetic, biodegradable scaffolds for a period of 8 days in rotisserie culture. Subsequently, cell-seeded scaffolds were exposed to physiologically relevant oscillatory shear stresses (overall mean, time-averaged shear stress, ~7.9 dynes/cm2; overall mean, oscillatory shear index, ~0.18) for an additional 2 weeks. The constructs were found to exhibit relatively augmented endothelial cell expression (CD31; compared to static controls) but concomitantly served to restrict the level of the activated smooth muscle phenotype (α-SMA) and also produced very low stem cell secretion levels of fibronectin (p < 0.05 compared to static and rotisserie controls). These findings suggest that fluid-induced oscillatory shear stresses alone are important in regulating a healthy valve phenotype of the engineered tissue matrix. Moreover, as solid stresses could lead to increased α-SMA levels, they should be excluded from conditioning during the culture process owing to their associated potential risks with pathological tissue remodeling. In conclusion, engineered valve tissues derived from mesenchymal stem cells revealed both a relatively robust valvular phenotype after exposure to physiologically relevant scales of oscillatory shear stress and may thereby serve to accelerate healthy valve tissue remodeling in the host post-implantation.
Highlights
Heart valve disease requires a largely singular treatment in the form of artificial valve replacement
MSCs are one of the most promising and suitable cell types for regeneration since they can differentiate into endothelial and interstitial-line cell subtypes, which reside in heart valves
Phenotypic matching of the implant with host tissues is an important attribute in subsequent de novo tissue remodeling in vivo, due to chemotactic events that are initiated by the implanted engineered extracellular matrix and cells, which may accelerate host tissue regeneration due to its niche [20]
Summary
Heart valve disease requires a largely singular treatment in the form of artificial valve replacement. Prosthetic valve replacement devices offer reasonable solutions; durability and risk factors are of concern. Mechanical heart valves are durable but carry increased risks of blood clotting and require life-long anticoagulation therapy, excluding them from patient subsets, such as children with critical congenital valve defects. In the case of pediatric critical congenital valvular diseases, no ideal treatment options exist as somatic growth is required to avoid multiple reoperations as the child grows; in addition small, sizing options [
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