Characterization of structural and signaling molecules by human valve interstitial cells and comparison to human mesenchymal stem cells.

Background And Aim Of The Study: Human mesenchymal stem cells (MSCs) are a potential cell source for the tissue engineering of biological structures, including cardiac valves. A comprehensive, phenotypic analysis of MSCs and, for the latter, their comparison with valve interstitial cells (ICs) is therefore essential.

Methods: Isolates of bone marrow-derived human MSCs and human cardiac valve ICs were extensively phenotyped for their expression of membrane proteins involved in adhesion and cell-cell communication, cytoskeletal components, extracellular matrix (ECM) proteins and gene expression of WNT/FZD/SFRP/DKK/LRP family members.

Results: MSCs and valve ICs (>80%) expressed fibroblast surface antigen, smooth muscle alpha-actin, vimentin and CD44; expression of MHC class I and II and calponin was inconsistent, and a small proportion expressed desmin and smooth muscle myosin. CD105 was weakly expressed by a low percentage of valve ICs (<10%) compared to MSCs (>90%). ECM components made by both cell types demonstrated similar levels and patterns of staining, although expression of elastin was not detected by both cell types. Adhesion molecule expression was highly variable among the MSC isolates and between the two cell types, with the predominant integrins being alphal, alpha3, alpha5, and beta1 by both cell types. PCR analysis of WNT/FZD/SFRP/LRP family members revealed a greater range of the WNT family of genes being expressed in MSCs compared to ICs.

Conclusion: The study results provided an extensive fingerprint of valve ICs and of MSCs for the tissue engineering of biological structures and for the manipulation of their desired phenotype. MSCs represent a promising cell type for valve tissue engineering, and will require extensive phenotyping after differentiation.