title: Cyclopentyladenosine improves cell proliferation, wound healing, and hair growth.
abstract: BACKGROUND
  N(6)-Cyclopentyladenosine (CPA), a structural analog of adenosine, is a vasodilator with extensive pharmacological effects. However, little is known about the effect of CPA on wound healing and hair growth.
  
  
  METHODS
  Cellular responses to CPA were measured in vitro by tetrazolium dye reduction and in vivo by bromodeoxyuridine (BrdU) uptake. The effect of CPA on healing of incisional and excisional wounds on the dorsum of diabetic (db/db, n = 94) and nondiabetic (db/+, n = 20) mice and hair growth along the wound margin was evaluated with wound breaking strength, wound closure rate, and quantitative histology.
  
  
  RESULTS
  CPA stimulated proliferation of BALB/3T3 fibroblasts and human dermal microvascular endothelial cells in both quiescent and nonquiescent phases. Wounds treated with CPA at 10 microM showed a significant increase in the number of BrdU-labeled cells, including keratinocytes, fibroblasts, endothelial cells, and cells in sebaceous glands and the outer root sheath of hair follicles, compared with controls (P < 0.05). CPA application (5.1 microg/daily for 12 days) significantly increased the breaking strength of incisional wounds at day 24 postwound (P < 0.05). Excisional wound closure rate in the CPA-treated group (3.4 microg/daily for 15 days) was accelerated starting at day 10 postwound compared with controls (P < 0.01). Tissue sections from CPA-treated wounds showed a sevenfold increase in hair follicle number, compared with controls (P < 0.01). Enhanced hair growth along the wound margin was revealed in CPA-treated groups.
  
  
  CONCLUSIONS
  CPA stimulated proliferation of many cell types in vivo and in vitro and enhanced wound healing and hair growth. Therefore, CPA could be an interesting candidate for clinical application.
authors.affiliation: Department of Surgery, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20852, USA. lsun@usuhs.mil
authors.forename: L L
authors.initials: LL
authors.lastname: Sun
authors.forename: L L
authors.initials: LL
authors.lastname: Xu
authors.forename: T B
authors.initials: TB
authors.lastname: Nielsen
authors.forename: P
authors.initials: P
authors.lastname: Rhee
authors.forename: D
authors.initials: D
authors.lastname: Burris
mesh_terms: D016475:3T3 Cells; D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D005260:Female; D018859:Hair Follicle / Q000187:drug effects* / Q000254:growth & development; D051379:Mice; D008810:Mice, Inbred C57BL; D014945:Wound Healing / Q000187:drug effects*
chemical_list: C048599:N(6)-cyclopentyladenosine; D001973:Bromodeoxyuridine; D000241:Adenosine