Feasibility of Human Skin Grafts on An Isolated But Accessible Vascular Supply on Athymic Rats As a System to Study Percutaneous Penetration and Cutaneous Injury
Abstract
The objective of this research is to determine the feasibility of grafting human skin onto congenitally athymic (nude) rats and to isolate the grafted human skin as a flap of functional skin onto an isolated, but accessible, vasculature. Thereafter, the proposed system is to be characterized as to structure and function of the skin and, finally, to be validated as a system for studying percutaneous absorption. During year 1, we confirmed that nude rats, are capable of immunologically rejecting human skin. They do not reject allogeneic (rat) skin grafts. Experiments have now demonstrated that a rather bizarre series of events leads to rejection of human skin grafts on nude rats more than 90% of the time. It appears that this rejection process is humorally (antibody) mediated and is directed at antigens that are not necessarily present in normal human skin prior to grafting, but which develop after engraftment. Low-dose cyclosporine at 25 mg/kg/day prolongs engraftment of human skin for more than 90 days after the cycloserine is discontinued. To validate the system as a method to study metabolism of topically-applied agents, we have used vidarabine (an anti-viral agent). These validation experiments, as well as the fact that human skin can be maintained on nude rats, suggest that this model system will be a significant tool in defining percutaneous absorption and toxicity of chemical agents.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 1986
- Accession Number
- ADA201679
Entities
People
- Gerald G. Krueger
- Lynn K. Pershing
Organizations
- University of Utah