Inhibition of wound closure by transforming growth factor‐β and dexamethasone in a fetal mouse limb organ culture model

Abstract

Tissue repair comprises several physiologic processes including the deposition of a newly synthesized connective tissue matrix and the regeneration of the epidermis by reepithelialization. A fetal mouse limb organ culture system facilitates the investigation of both reepithelialization and connective tissue deposition in repair within a controlled environment. A sutured closed wound in an intact 18.5-day old fetal mouse limb completely heals by 7 days. Including dexamethasone in the media inhibited both reepithelialization and connective tissue deposition. Concurrent administration of transforming growth factor-beta with dexamethasone restored the deposition of connective tissue but did not restore reepithelialization. When transforming growth factor-beta was given alone, connective tissue deposition was enhanced at both the wound site and in contiguous dermis, but reepithelialization did not proceed. Transforming growth factor-beta inhibited wound closure by blocking the migration of epidermal cells. The organ-cultured, wounded fetal mouse limb system is sufficiently sensitive to show both mesenchymal cell-enhancing activity as well as epithelial migration inhibiting activity by transforming growth factor-beta. The in vitro repair of fetal mouse limbs may serve as an in vitro system to test the influence of soluble agents on the repair process.