title: Visible effects of rapamycin (sirolimus) on human skin explants in vitro.
abstract: In this manuscript, we report observations of the effects of rapamycin in an organotypic culture of human skin explants. The tissues were cultured for 5 days at the air-liquid interface or in submersed conditions with media with and without rapamycin at 2 nM concentration. Histological analysis of tissue sections indicated that rapamycin-treated samples maintained a better epidermal structure in the upper layers of the tissue than untreated samples, mostly evident when skin was cultured in submersed conditions. A significant decrease in the number of positive proliferative cells using the Ki67 antigen was observed when specimens were treated with rapamycin, in both air-liquid and submersed conditions but apoptosis differences between treated and untreated specimens, as seen by cleaved caspase-3 positive cells, were only observed in submersed specimens. Finally, a decrease and variability in the location in the expression of the differentiation marker involucrin and in E-cadherin were also evident in submersed samples. These results suggest that the development of topical applications containing rapamycin, instead of systemic delivery, may be a useful tool in the treatment of skin diseases that require reduction of proliferation and modulation or control of keratinocyte differentiation.
authors.affiliation: Section of Plastic Surgery, Department of Surgery, University of Michigan, 1150 W. Medical Drive, Ann Arbor, MI 48109, USA. aperamo@hushmail.com
authors.forename: Antonio
authors.initials: A
authors.lastname: Peramo
authors.forename: Cynthia L
authors.initials: CL
authors.lastname: Marcelo
mesh_terms: D000287:Administration, Topical; D017209:Apoptosis / Q000187:drug effects; D015820:Cadherins / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects* / Q000473:pathology; D019394:Ki-67 Antigen / Q000378:metabolism; D009924:Organ Culture Techniques; D011498:Protein Precursors / Q000378:metabolism; D020123:Sirolimus / Q000008:administration & dosage*; D012867:Skin / Q000187:drug effects* / Q000473:pathology; D012871:Skin Diseases / Q000188:drug therapy*; D016038:Skin Transplantation; D023822:Tissue Engineering
chemical_list: D015820:Cadherins; D019394:Ki-67 Antigen; D011498:Protein Precursors; C032253:involucrin; D053148:Caspase 3; D020123:Sirolimus