title: Potential use of skin-derived precursors (SKPs) in establishing a cell-based treatment model for Hirschsprung's disease.
abstract: BACKGROUND
  Hirschsprung's (HSCR) disease is characterized by absence of ganglia in the distant bowel. Skin-derived precursor cells (SKPs) are somatic stem cells located in the bulge of hair follicles with high neural plasticity. In this study, we elucidated the therapeutic potential of SKPs for replenishing absent ganglia in HSCR bowel.
  
  
  METHODS
  SKPs were isolated from mouse or human skin and cultured in neural differentiation medium to generate various types of neural cells. Expression of stem cell and neural differentiation markers were monitored by reverse-transcription polymerase chain reaction and immunocytochemistry, respectively. Engraftment and differentiation potentials of SKPs were further assessed using ex vivo gut culture with Ret(k/k) aganglionic gut.
  
  
  RESULTS
  Expression studies revealed that SKPs express a panel of neural crest markers and three key stemness factors (Klf4, c-Myc and Sox2), which may account for the multipotency of these cells. Subsequent differentiation assays directly demonstrated that both mouse and human SKPs retain high differentiation capacities to form enteric neurons, and glia. Importantly, with ex vivo gut explants assay, we further showed that SKPs colonize and differentiate in the Ret(k/k) aganglionic hindgut explants.
  
  
  CONCLUSIONS
  Our data suggest that SKPs may represent an alternative source of stem cells for the study of cell-based therapy for HSCR.
authors.affiliation: Department of Surgery, Li Ka Shing Faculty of Medicine, University of Hong Kong, Pokfulam, Hong Kong.
authors.forename: Carmen Ka-Man
authors.initials: CK
authors.lastname: Kwok
authors.forename: Paul Kwong-Hang
authors.initials: PK
authors.lastname: Tam
authors.forename: Elly Sau-Wai
authors.initials: ES
authors.lastname: Ngan
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D006627:Hirschsprung Disease / Q000601:surgery*; D006801:Humans; D007223:Infant; D000090062:Kruppel-Like Factor 4; D051379:Mice; D008954:Models, Biological; D012867:Skin / Q000166:cytology*; D033581:Stem Cell Transplantation