Mechanical stress and cell-scaffold interactions in tissue-engineered heart valves upregulate genes associated with endochondral ossification, which may predispose the grafts to calcification.
Mechanical deformation may predispose tissue-engineered valves to calcification; leaves open optimal conditioning for durable grafts.
Tissue-engineered heart valves are prone to early structural deterioration. We hypothesize that cell-scaffold interaction and mechanical deformation results in upregulation of genes related to osteogenic/chondrogenic differentiation and thus changes extracellular matrix (ECM) composition in human bone marrow mesenchymal stem cell (hBMSC)-derived tissue-engineered grafts. hBMSC were expanded and seeded onto poly-glycolic acid/poly-lactic acid scaffold for 14 days. Seeded tissue-engineered constructs (TEC) were subjected to cyclic flexure for 24 h, whereas control TEC was maintained in roller bottles for the same duration. hBMSC, TEC, and mechanically deformed TEC were subjected to gene-array and histological analysis. Expression levels of RNA and/or protein markers related to chondrogenesis (Sox9, MGP, RunX2, Col II, Col X, and Col XI) and osteogenesis (ALPL, BMP2, EDN1, RunX1, and Col I) were increased in TEC compared to unseeded hBMSC. Histological sections of TEC stained positive for Saffranin O, alkaline phosphatase activity, and calcium deposits. The expression levels of the above gene and protein markers further increased in deformed TEC compared to static TEC. Cell-scaffold interactions and mechanical stress results in gene expression suggestive of endochondral-ossification that impact upon ECM composition and may predispose them to eventual calcification.
No takes yet. Share an insight, caveat, or question.
Emani et al. (2011) studied this question.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: