The research is directed toward a clearer understanding of the dynamic processes of epidermal regeneration and dermal repair, especially during healing. The skin continually maintains and restores itself during normal tissue turnover. After injury the process of restoration is particularly pronounced and may include activities not present under resting conditions, as well as an increase in homeostatic activities. Healing occurs in response to any tissue perturbation suggesting that many chronic diseases are partially a problem of incomplete or abnormal healing. Platelet-derived factors (PDFs) have dramatic effects on connective tissue cells in culture and may play an important role in the skin's healing response. PDFs have been described that are specific for dermal fibroblasts and other connective tissue cells, but none have been found which affect epidermal cells. The investigator has identified a platelet homogenate fraction (PHF) that both supports and stimulates epidermal cells in explant culture. (Explant cultures are split-thickness sections of skin made of epidermis and the most superficial papillary dermis.) PHF has been separated into two active fractions and each has a different effect on epidermal cells. The two fractions are distinct from PDFs that are now known.
The specific aims of this proposal are 1) to complete the isolation and characterization of the factors in PHF affecting epidermal cells, 2) to learn whether these factors act directly on the epidermis or indirectly through dermal elements, 3) to learns how epidermal cellular events (migration, mitosis and maturation) are influenced by PHF factors, 4) to study the effects of these factors on the healing process after a cut wound, 5) to study their effects on healing after a burn wound, which shows an unexplained delay in healing, perhaps due to the absence of PDFs. PHF will be fractionated and characterized using standard techniques that have been successfully applied to other PDFs, including chromatography, subcellular fractionation, gel electrophoresis and inactivation by enzymatic, chemical and physical conditions. The resultant fractions will be studied in vitro using pig and human skin to prepare both explants and primary epidermal cell cultures (which exclude dermal influences). Wound healing will be studied in established experimental porcine models. This research will provide new information about physiological factors from platelets and how they are involved in cutaneous biology and repair processes.
| Kane, C J; Hebda, P A; Mansbridge, J N et al. (1991) Direct evidence for spatial and temporal regulation of transforming growth factor beta 1 expression during cutaneous wound healing. J Cell Physiol 148:157-73 |
| Hebda, P A (1988) Stimulatory effects of transforming growth factor-beta and epidermal growth factor on epidermal cell outgrowth from porcine skin explant cultures. J Invest Dermatol 91:440-5 |
