title: Tissue response and Msx1 expression after human fetal digit tip amputation in vitro.
abstract: Regeneration of mammalian digit tips is well described; however, associated cellular or molecular events have not been studied in humans. We describe an in vitro human fetal model of response to digit tip amputation, and report expression of the transcription repressor Msx1 in the developing and regrowing human digit tip. Human fetal digits from specimens ranging from 53 to 117 days' estimated gestational age (EGA) were cultured in a defined serum-free medium with supplemented oxygen for time periods from 4 days to 4 weeks. Histology and immunohistochemistry were performed on paired control and tip-amputated digits. Regrowing tissue covered the cut end of the distal phalanx in digits up to 80 days' EGA. Msx1 expression was detected beneath the nail field in control digits to at least 70 days' EGA and at the regrowing tip of 57-day digits at 4 and 7 days post-amputation. Our results show that human fetal digits regrow tissue in vitro in response to tip amputation. This process appears spatially associated with Msx1 expression. Msx1 expression appears increased at the regrowing tip of 57-day digits by 4 days after amputation.
authors.affiliation: Department of Orthopaedics and Sports Medicine, University of Washington School of Medicine--Harborview Medical Center, Seattle, Washington 98104, USA. callan@u.washington.edu
authors.forename: Christopher H
authors.initials: CH
authors.lastname: Allan
authors.forename: Philip
authors.initials: P
authors.lastname: Fleckman
authors.forename: Russell J
authors.initials: RJ
authors.lastname: Fernandes
authors.forename: Barbara
authors.initials: B
authors.lastname: Hager
authors.forename: Jennifer
authors.initials: J
authors.lastname: James
authors.forename: Zudtky
authors.initials: Z
authors.lastname: Wisecarver
authors.forename: F Kyle
authors.initials: FK
authors.lastname: Satterstrom
authors.forename: Alicia
authors.initials: A
authors.lastname: Gutierrez
authors.forename: Anthony
authors.initials: A
authors.lastname: Norman
authors.forename: Anna
authors.initials: A
authors.lastname: Pirrone
authors.forename: Robert A
authors.initials: RA
authors.lastname: Underwood
authors.forename: Brian P
authors.initials: BP
authors.lastname: Rubin
authors.forename: Miqin
authors.initials: M
authors.lastname: Zhang
authors.forename: Hassna R
authors.initials: HR
authors.lastname: Ramay
authors.forename: John M
authors.initials: JM
authors.lastname: Clark
mesh_terms: D000673:Amputation, Traumatic / Q000378:metabolism* / Q000503:physiopathology*; D005333:Fetus; D005385:Fingers / Q000196:embryology / Q000503:physiopathology*; D005865:Gestational Age; D006801:Humans; D051957:MSX1 Transcription Factor / Q000378:metabolism*; D012038:Regeneration / Q000502:physiology*; D013997:Time Factors; D046509:Tissue Culture Techniques; D014945:Wound Healing / Q000502:physiology
chemical_list: D051957:MSX1 Transcription Factor