title: A novel aldehyde dehydrogenase-3 activator leads to adult salivary stem cell enrichment in vivo.
abstract: OBJECTIVE
  To assess aldehyde dehydrogenase (ALDH) expression in adult human and murine submandibular gland (SMG) stem cells and to determine the effect of ALDH3 activation in SMG stem cell enrichment.
  
  
  METHODS
  Adult human and murine SMG stem cells were selected by cell surface markers (CD34 for human and c-Kit for mouse) and characterized for various other stem cell surface markers by flow cytometry and ALDH isozymes expression by quantitative reverse transcriptase PCR. Sphere formation and bromodeoxyuridine (BrdUrd) incorporation assays were used on selected cells to confirm their renewal capacity and three-dimensional (3D) collagen matrix culture was applied to observe differentiation. To determine whether ALDH3 activation would increase stem cell yield, adult mice were infused with a novel ALDH3 activator (Alda-89) or with vehicle followed by quantification of c-Kit(+)/CD90(+) SMG stem cells and BrdUrd(+) salispheres.
  
  
  RESULTS
  More than 99% of CD34(+) huSMG stem cells stained positive for c-Kit, CD90 and 70% colocalized with CD44, Nestin. Similarly, 73.8% c-Kit(+) mSMG stem cells colocalized with Sca-1, whereas 80.7% with CD90. Functionally, these cells formed BrdUrd(+) salispheres, which differentiated into acinar- and ductal-like structures when cultured in 3D collagen. Both adult human and murine SMG stem cells showed higher expression of ALDH3 than in their non-stem cells and 84% of these cells have measurable ALDH1 activity. Alda-89 infusion in adult mice significantly increased c-Kit(+)/CD90(+) SMG population and BrdUrd(+) sphere formation compared with control.
  
  
  CONCLUSIONS
  This is the first study to characterize expression of different ALDH isozymes in SMG stem cells. In vivo activation of ALDH3 can increase SMG stem cell yield, thus providing a novel means for SMG stem cell enrichment for future stem cell therapy.
authors: Department of Radiation Oncology, Stanford University, California, 94305, USA.
authors: Alice
authors: A
authors: Banh
authors: Nan
authors: N
authors: Xiao
authors: Hongbin
authors: H
authors: Cao
authors: Che-Hong
authors: CH
authors: Chen
authors: Peiwen
authors: P
authors: Kuo
authors: Trevor
authors: T
authors: Krakow
authors: Brindha
authors: B
authors: Bavan
authors: Brian
authors: B
authors: Khong
authors: Mike
authors: M
authors: Yao
authors: Chi
authors: C
authors: Ha
authors: Michael J
authors: MJ
authors: Kaplan
authors: Davud
authors: D
authors: Sirjani
authors: Kristin
authors: K
authors: Jensen
authors: Christina S
authors: CS
authors: Kong
authors: Daria
authors: D
authors: Mochly-Rosen
authors: Albert C
authors: AC
authors: Koong
authors: Quynh-Thu
authors: QT
authors: Le
mesh_terms: D053687:Adult Stem Cells / Q000166:cytology* / Q000201:enzymology*; D000444:Aldehyde Dehydrogenase / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D000498:Allyl Compounds / Q000494:pharmacology*; D000818:Animals; D018952:Antigens, CD34 / Q000032:analysis; D000950:Antigens, Ly / Q000032:analysis; D052117:Benzodioxoles / Q000494:pharmacology*; D001973:Bromodeoxyuridine / Q000378:metabolism; D004789:Enzyme Activation; D020536:Enzyme Activators / Q000494:pharmacology*; D006258:Head and Neck Neoplasms / Q000532:radiotherapy; D006801:Humans; D018960:Hyaluronan Receptors / Q000032:analysis; D008565:Membrane Proteins / Q000032:analysis; D051379:Mice; D008810:Mice, Inbred C57BL; D019009:Proto-Oncogene Proteins c-kit / Q000032:analysis; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D013363:Submandibular Gland / Q000166:cytology* / Q000378:metabolism; D018800:Thy-1 Antigens / Q000032:analysis; D014987:Xerostomia / Q000209:etiology
chemical_list: C571663:5-allyl-1,3-benzodioxol; D000498:Allyl Compounds; D018952:Antigens, CD34; D000950:Antigens, Ly; D052117:Benzodioxoles; D020536:Enzyme Activators; D018960:Hyaluronan Receptors; C074650:Ly6a protein, mouse; D008565:Membrane Proteins; D012333:RNA, Messenger; D018800:Thy-1 Antigens; C030863:corneal protein 54, bovine; D000444:Aldehyde Dehydrogenase; D019009:Proto-Oncogene Proteins c-kit; D001973:Bromodeoxyuridine