INHIBITING THE DIFFERENTIATION OF MYOCARDIOCYTES BY HYALURONIC-ACID

Background. In vitro experimentation found that wounded midgestation f etal mouse hearts heal scarlessly. Scarless repair occurs in an enviro nment enriched in hyaluronic acid (HA), while in the absence of HA and the inclusion of hyaluronidase (HAdase), repair by scarring occurs. E xcess HA downregulates the expression of the specific HA receptor, RHA MM (receptor for HA-mediated motility). The expression of RHAMM and th e migration of cardiac cells from fetal heart explants were investigat ed in the presence of excess HA and added HAdase. Method. Hearts from Gestational Day 15 fetal mice (term = 20) were cut into four fragments , established as explant cultures, and assigned to one of three treatm ent groups: 400 mu g/ml HA, 50 U/ml HAdase, or saline. Cellular outgro wth was recorded at Day 7. The character of the migrating cells (fibro blast-like or myocardiocyte) was determined by immunostaining for fila mentous actin (f-actin, microfilaments) or desmin (intermediate filame nts). The expression of RHAMM was documented also. Results. The inclus ions of HA stimulated cell migration and proliferation, perpetuated ce lls as immature myocardiocytes, and blocked the expression of RHAMM. T he inclusion of HAdase limited cell migration and proliferation, promo ted the differentiation of cells into myocardiocytes, and increased th e number of cells expressing RHAMM. Conclusion. Increased concentratio ns of HA promoted the proliferation and migration of an immature popul ation of myocardiocytes. On the other hand the inclusion of HAdase inh ibits the migration and proliferation of cells and promotes the appear ance of myocardiocytes with a fibroblast-like morphology. The speculat ion is that excess HA may promote proliferation and migration of immat ure myocardiocytes into a heart defect, leading to replacement of lost myocardium with contractile tissue rather than dysfunctional scar, (C ) 1998 Academic Press.