Cell Division is a Determinant of Cell Motility in Activated Single Heart Valve Interstitial Cells In Vitro

Although valve interstitial cells (VIC) are most important in the repair of heart valves in response to disease, little is known about the cell biology of VIC repair in order to identify possible therapeutic targets to regulate repair. Since VICs show single cell motility during repair, we used low‐density monolayer cultures to study the determinants of motility in single porcine VICs which express α‐smooth muscle actin. We categorized the morphology of these activated single VICs into six distinct types which were reminiscent of cell shapes seen ultrastructurally during in vivo valve repair. Of these morphologies, round, rhomboid, tailed and spindled‐shaped VICs were most common. Using time‐lapse imaging and confocal immunofluorescent microscopy, we showed that tailed and spindle‐shaped VICs were the predominant motile types and had fewer focal adhesions and extracellular fibronectin fibrils than round and rhomboid shaped VICs which were less motile and showed prominent focal adhesions and extracellular fibronectin fibrils. An important finding was that mitosis was an important determinant of VIC migration. Time‐lapse imaging showed that many motile VICs were observed to be separating daughter cells migrating as tailed and spindle‐shaped cells. Cell division is an important factor in determining specific VIC morphologies which promote motility and could be a therapeutic target to regulate valve repair.