REGENERATIVE HEALING OF INCISIONAL WOUNDS IN MIDGESTATIONAL MURINE HEARTS IN ORGAN-CULTURE

Objective: Using an organ-culture fetal heart repair model, we explore d fetal repair in tissues other than dermis. Methods: Wounded fetal mo use hearts of 14 and 18 days' gestation (term = 20 days), as well as h earts of 22 days' gestation (newborn), were maintained in serum-free m edium, Specimens were fixed at 2, 7, and 11 days and then processed fo r histologic examination. Small fragments of fetal hearts from all tim e points were cultured as explants, The migration of cells from the pe riphery of the explants was compared at day 4, and the pattern of micr ofilaments in these cells was assessed, Results: In 14-day hearts (n = 18), tissue architecture was rapidly reestablished without an inflamm atory response or scarring, constituting regenerative repair. In 18-da y hearts (n = 18), no reestablishment of muscle fibers or wound closur e occurred, In the 22-day explants (n = 12) the wounds closed by scarr ing, Cell migration from 14-day explants was 4.7 +/- 2.3 ocular units; from 18-day explants, it was 2.6 +/- 1.1 ocular units; and from 22-da y explants, it was 0.9 +/- 0.4 ocular units, Microfilaments of 14-day cells were arranged at the periphery of the cell consistent with cardi omyocytes, Microfilaments of 18- and 22-day cells were arranged in par allel arrays (stress fibers) that were consistent with fibroblasts. Co nclusions: We propose that regenerative healing of 14-day fetal hearts is by the migration of cardiomyocytes. At 18 and 22 days, cardiomyocy tes are too differentiated and unable to migrate; hence cell migration is limited to resident fibroblasts, which are deficient at 18 days bu t sufficient at 21 days to be repaired by the scarring process.