title: Preclinical safety studies on autologous cultured human skin fibroblast transplantation.
abstract: Recently, FDA approved the clinical use of autologous fibroblasts (LAVIV™) for the improvement of nasolabial fold wrinkles in adults. The use of autologous fibroblasts for the augmentation of dermal and subcutaneous defects represents a potentially exciting natural alternative to the use of other filler materials for its long-term corrective ability and absence of allergic adverse effects proved by clinical application. However, compared to the clinical evidence, preclinical studies are far from enough. In this study, human skin-derived fibroblasts were cultured and expanded for both in vitro and in vivo observations. In vitro, the subcultured fibroblasts were divided into two groups. One set of cells underwent cell cycle and karyotype analysis at passages 5 and 10. The second group of cells was cocultured in medium with different concentrations of human skin extract D for the measurement of collagen concentration and cell count. In vivo, the subcultured fibroblasts were injected into nude mice subcutaneously. Biopsies were taken for morphology observation and specific collagen staining at 1, 2, and 3 months after injection. The results in vitro showed no significant differences in cell cycle distribution between passages 5 and 10. Cell proliferation and secretion were inhibited as the concentration of extract D increased. In vivo, the fibroblasts were remarkably denser on the experimental side with no dysplastic cells. Mitotic cells were easily observed at the end of the first month but were rare at the end of the third month. Type III collagen was detected at the end of the first month, while collagen type I was positive at the end of the second month. The content of both collagens increased as time passed. The above results indicated that the use of the autologous fibroblasts was safe, providing a basic support for clinical use of fibroblasts.
authors.affiliation: Department of the Plastic and Reconstructive Surgery, Clinical Division of Surgery, Chinese People's Liberation Army (PLA) General Hospital, Beijing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zeng
authors.forename: Shuying
authors.initials: S
authors.lastname: Zhang
authors.forename: Dai
authors.initials: D
authors.lastname: Liu
authors.forename: Mi
authors.initials: M
authors.lastname: Chai
authors.forename: Jiaqi
authors.initials: J
authors.lastname: Wang
authors.forename: Yuming
authors.initials: Y
authors.lastname: Zhao
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D018929:Cell Culture Techniques / Q000379:methods; D017690:Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000637:transplantation*; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D012867:Skin / Q000166:cytology*; D014182:Transplantation, Autologous; D055815:Young Adult