title: Spermidine promotes human hair growth and is a novel modulator of human epithelial stem cell functions.
abstract: BACKGROUND
  Rapidly regenerating tissues need sufficient polyamine synthesis. Since the hair follicle (HF) is a highly proliferative mini-organ, polyamines may also be important for normal hair growth. However, the role of polyamines in human HF biology and their effect on HF epithelial stem cells in situ remains largely unknown.
  
  
  RESULTS
  We have studied the effects of the prototypic polyamine, spermidine (0.1-1 µM), on human scalp HFs and human HF epithelial stem cells in serum-free organ culture. Under these conditions, spermidine promoted hair shaft elongation and prolonged hair growth (anagen). Spermidine also upregulated expression of the epithelial stem cell-associated keratins K15 and K19, and dose-dependently modulated K15 promoter activity in situ and the colony forming efficiency, proliferation and K15 expression of isolated human K15-GFP+ cells in vitro. Inhibiting the rate-limiting enzyme of polyamine synthesis, ornithine decarboyxlase (ODC), downregulated intrafollicular K15 expression. In primary human epidermal keratinocytes, spermidine slightly promoted entry into the S/G2-M phases of the cell cycle. By microarray analysis of human HF mRNA extracts, spermidine upregulated several key target genes implicated e.g. in the control of cell adherence and migration (POP3), or endoplasmic reticulum and mitochondrial functions (SYVN1, NACA and SLC25A3). Excess spermidine may restrict further intrafollicular polyamine synthesis by inhibiting ODC gene and protein expression in the HF's companion layer in situ.
  
  
  CONCLUSIONS
  These physiologically and clinically relevant data provide the first direct evidence that spermidine is a potent stimulator of human hair growth and a previously unknown modulator of human epithelial stem cell biology.
authors.affiliation: Department of Dermatology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Yuval
authors.initials: Y
authors.lastname: Ramot
authors.forename: Stephan
authors.initials: S
authors.lastname: Tiede
authors.forename: Tamás
authors.initials: T
authors.lastname: Bíró
authors.forename: Mohd Hilmi
authors.initials: MH
authors.lastname: Abu Bakar
authors.forename: Koji
authors.initials: K
authors.lastname: Sugawara
authors.forename: Michael P
authors.initials: MP
authors.lastname: Philpott
authors.forename: Wesley
authors.initials: W
authors.lastname: Harrison
authors.forename: Marko
authors.initials: M
authors.lastname: Pietilä
authors.forename: Ralf
authors.initials: R
authors.lastname: Paus
mesh_terms: D049109:Cell Proliferation / Q000187:drug effects; D002469:Cell Separation; D003114:Colony-Forming Units Assay; D000078404:Epidermal Cells; D004847:Epithelial Cells / Q000166:cytology*; D005260:Female; D020869:Gene Expression Profiling; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006197:Hair / Q000187:drug effects* / Q000254:growth & development*; D018859:Hair Follicle / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D007633:Keratins / Q000235:genetics / Q000378:metabolism; D009955:Ornithine Decarboxylase / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D013095:Spermidine / Q000494:pharmacology*; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D049452:Green Fluorescent Proteins; D007633:Keratins; D009955:Ornithine Decarboxylase; D013095:Spermidine