Phenotypic and functional characterization of interstitial cells from human heart valves, pericardium and skin

Human heart valve interstitial cells (ICs) have been understudied to date. The aim of this study was to determine whether valve ICs were uniquely different from pericardial ICs and skin fibroblasts by determining their phenotype and investigating their reactivity.

ICs were cultured from human heart valves (n = 13), pericardium (n = 4) and skin (n = 4). Cell phenotype was determined by immunofluorescence using a panel of antibodies against surface and cytoskeletal components, and intracellular calcium changes were evaluated by loading the cells with fura-2 acetoxymethyl ester.

Skin fibroblasts expressed virtually no smooth muscle (SM) alpha-actin, whereas, 56.9+/-8.9% (mean +/- SEM) of ICs from valves and 21+/-7.6% of ICs from pericardium expressed SM alpha-actin. ICs from pericardium and skin fibroblasts always expressed a fibroblast surface antigen, whereas expression was variable on valve ICs (80+/-6.9%). All cells expressed prolyl 4-hydroxylase, beta-tubulin and vimentin, but not desmin. Transient increases in intracellular calcium were induced by vasoactive agents: skin fibroblasts were least responsive to all agents.

ICs cultured from heart valves consist of a mixed population of specific cell types, many of which express SM alpha-actin and may be classified as myofibroblasts. The intracellular calcium responses to vasoactive agents indicated that a number of receptor signaling pathways existed. Evaluation of these may help to elucidate the role of myofibroblasts and other fibroblast phenotypes in valve function/dysfunction, as well as contribute to the development of tissue-engineered valves.