Hair Growth in Human Split-Thickness Skin Grafts Transplanted onto Nude Rats: The Role of Ciclosporin

Abstract

To date there have been no descriptions of hair growth following transplantation of human split-thickness skin grafts (HSTSG) to congenitally athymic (nude) mice or rats. Recently, we noted hair growth in HSTSG from scalp skin (HSTSG-SS) transplanted onto rats treated with ciclosporin (CS). By definition HSTSG-SS of 0.4 mm had all the anagen hairs cut from the papillae. Two months after engraftment, there was histological evidence of the formation of new papillae. Density of hair correlated with thickness of HSTSG, i.e. there were more hairs/square centimeter in HSTSG-SS of 1 mm thickness than in those of 0.4 mm thickness. New hairs appeared on an average of 1 cm²/week in HSTSG-SS that were 1 mm thick; by 10 weeks, the mean density was 7.9 hairs/cm². In the thinner grafts, the density was 3.5 hairs/cm² (p < 0.025). The rate of growth in the thicker grafts ranged from 0 to 0.25 mm/day, with an average of 0.1 mm/day. At 10 weeks after grafting, the hairs had a mean length of 4.4 mm in the thicker and 1.7 mm in the thinner grafts (p < 0.001). The average diameter of the hair shafts was 0.05 mm at the various times tested. These observations identify a previously unrecognized process of hair growth and present an in vivo model to study human hair growth process, including the role of CS in hair growth.

Reconstructed human skin shows epidermal invagination towards integrated neopapillae indicating early hair follicle formation in vitro

“…In contrast, human hair follicles are described to exist in two steady states called the active anagen (lasting years) and dormant telogen (lasting months) phases, which are separated by the transition phases catagen (regression) and neogen (regeneration; Al‐Nuaimi, Goodfellow, Paus, & Baier, 2012; Bernard, 2012; Halloy, Bernard, Loussouarn, & Goldbeter, 2000). In order to create a more human‐like model, human skin has been transplanted onto mice (Gilhar, Etzioni, & Krueger, 1990; Jahoda, Oliver, Reynolds, Forrester, & Horne, 1996). For example, adult human hair follicle neogenesis was observed when human neopapillae spheroids were first incorporated into human skin explants and then transplanted onto mice (Higgins, Chen, Cerise, Jahoda, & Christiano, 2013).…”

Development of humanized mouse and rat models with full-thickness human skin and autologous immune cells

“…Full-thickness human fetal skin readily engrafts onto immunodeficient mice, and develops into adult-like skin, in part due to the high regenerative capability and low MHC I and II expression, reducing the immunogenicity of the fetal skin compared to adult skin 34,35 . Furthermore, reports demonstrate that nude rats (moderate immunodeficiency) support human skin (split-thickness skin) engraftment and development, albeit host-mediated immune rejection occurs within a few months [36][37][38] . Although several rodent models demonstrate human skin engraftment and development, said platforms have not been coupled to autologous human immune cells and lymphoid tissues, such as in the hSIS-humanized SRG rodent models.…”

Towards human organ generation using interspecies blastocyst complementation: Challenges and perspectives for therapy

“…These rats exhibited moderate immunodeficiency characterized by loss of lymphocyte counts with age but sustained high counts for neutrophils, eosinophils, and monocytes. Therefore, this model could only support adult human skin grafts for a short time before host-mediated rejection ( Brüngger et al, 1984 ; Gilhar et al, 1986 ; 1990 ). Human CD45 + cells were detected in various rat tissues, such as the liver, thymus, kidney, spleen, etc., up to 6 months post-in-utero cord blood transplantation ( Sun et al, 2007 ).…”