title: Antioxidants cause rapid expansion of human adipose-derived mesenchymal stem cells via CDK and CDK inhibitor regulation.
abstract: BACKGROUND
  Antioxidants have been shown to enhance the proliferation of adipose-derived mesenchymal stem cells (ADMSCs) in vitro, although the detailed mechanism(s) and potential side effects are not fully understood.
  
  
  RESULTS
  During log-phase growth, exposure to ImF-A resulted in a higher percentage of ADMSCs in the S phase of the cell cycle and a smaller percentage in G0/G1 phase. This resulted in a significantly reduced cell-doubling time and increased number of cells in the antioxidant-supplemented cultures compared with those supplemented with FGF-2 alone, an approximately 225% higher cell density after 7 days. Western blotting showed that the levels of the CDK inhibitors p21 and p27 decreased after ImF-A treatment, whereas CDK2, CDK4, and CDC2 levels clearly increased. In addition, ImF-A resulted in significant reduction in the expression of CD29, CD90, and CD105, whereas relative telomere length, osteogenesis, adipogenesis, and chondrogenesis were enhanced. The results were similar for ADMSCs treated with antioxidants and those under hypoxic conditions.
  
  
  CONCLUSIONS
  Antioxidant treatment promotes entry of ADMSCs into the S phase by suppressing cyclin-dependent kinase inhibitors and results in rapid cell proliferation similar to that observed under hypoxic conditions.
authors.forename: Li-Yi
authors.initials: LY
authors.lastname: Sun
authors.forename: Cheng-Yoong
authors.initials: CY
authors.lastname: Pang
authors.forename: Dian-Kun
authors.initials: DK
authors.lastname: Li
authors.forename: Chia-Hsin
authors.initials: CH
authors.lastname: Liao
authors.forename: Wei-Chao
authors.initials: WC
authors.lastname: Huang
authors.forename: Chao-Chuan
authors.initials: CC
authors.lastname: Wu
authors.forename: Yi-Yo
authors.initials: YY
authors.lastname: Chou
authors.forename: Wei Wu
authors.initials: WW
authors.lastname: Li
authors.forename: Shin-Yuan
authors.initials: SY
authors.lastname: Chen
authors.forename: Hwan-Wun
authors.initials: HW
authors.lastname: Liu
authors.forename: Yao-Jen
authors.initials: YJ
authors.lastname: Chang
authors.forename: Ching-Feng
authors.initials: CF
authors.lastname: Cheng
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D000975:Antioxidants / Q000008:administration & dosage*; D016203:CDC2 Protein Kinase; D002455:Cell Division / Q000187:drug effects; D015687:Cell Hypoxia / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects*; D051358:Cyclin-Dependent Kinase 4 / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D016222:Fibroblast Growth Factor 2 / Q000096:biosynthesis; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects*
chemical_list: D000975:Antioxidants; D016222:Fibroblast Growth Factor 2; D016203:CDC2 Protein Kinase; C528899:CDK1 protein, human; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases
references.citation: Neurosurgery. 2010 Aug;67(2):357-65; discussion 365-6
references.pmid: 20644422
references.citation: Stem Cells Dev. 2005 Feb;14(1):92-102
references.pmid: 15725748
references.citation: Endocrinology. 1997 Oct;138(10):4456-62
references.pmid: 9322963
references.citation: Life Sci. 2011 Aug 15;89(7-8):250-8
references.pmid: 21722651
references.citation: J Cell Biochem. 2011 Mar;112(3):804-17
references.pmid: 21328454
references.citation: Stem Cells. 2010 Mar 31;28(3):555-63
references.pmid: 20073042
references.citation: PLoS One. 2012;7(3):e33742
references.pmid: 22470469
references.citation: Cell Tissue Res. 2007 Mar;327(3):449-62
references.pmid: 17053900
references.citation: J Neurochem. 2008 Aug;106(3):1017-26
references.pmid: 18419761
references.citation: Biomed Res. 2010 Feb;31(1):27-34
references.pmid: 20203417
references.citation: J Orthop Res. 2012 Feb;30(2):260-6
references.pmid: 21809383
references.citation: Stem Cells. 2006 Oct;24(10):2202-8
references.pmid: 16778152
references.citation: Cell Biochem Funct. 2008 Aug;26(6):664-75
references.pmid: 18636461
references.citation: J Cell Physiol. 2005 May;203(2):398-409
references.pmid: 15521064
references.citation: Stem Cells. 2008 Aug;26(8):2173-82
references.pmid: 18511601
references.citation: Curr Opin Chem Biol. 2007 Aug;11(4):394-8
references.pmid: 17656148
references.citation: Biochem Biophys Res Commun. 2012 Jan 6;417(1):305-10
references.pmid: 22155244
references.citation: Cytotherapy. 2011 Jul;13(6):675-85
references.pmid: 21231804
references.citation: Cell Physiol Biochem. 2004;14(4-6):311-24
references.pmid: 15319535
references.citation: Bioelectromagnetics. 2009 May;30(4):251-60
references.pmid: 19204973
references.citation: Nucleic Acids Res. 2002 May 15;30(10):e47
references.pmid: 12000852
references.citation: Biochem Biophys Res Commun. 2010 Oct 29;401(4):509-15
references.pmid: 20869949
references.citation: Hum Cell. 2010 Nov;23(4):152-5
references.pmid: 21166886
references.citation: Biotechnol Appl Biochem. 2008 Dec;51(Pt 4):159-66
references.pmid: 18279148
references.citation: J Biosci Bioeng. 2005 Jul;100(1):12-27
references.pmid: 16233846
references.citation: Stem Cell Res Ther. 2012 Mar 02;3(2):9
references.pmid: 22385573
references.citation: Eur J Haematol. 2006 Apr;76(4):309-16
references.pmid: 16519702
references.citation: Circulation. 2004 Mar 16;109(10):1292-8
references.pmid: 14993122
references.citation: Cell Prolif. 2010 Oct;43(5):445-56
references.pmid: 20887551
references.citation: PLoS One. 2007 May 02;2(5):e416
references.pmid: 17476338
references.citation: Blood. 2011 Jan 13;117(2):459-69
references.pmid: 20952688
references.citation: Cells Tissues Organs. 2010;192(2):106-15
references.pmid: 20185896
references.citation: Blood. 2004 Mar 1;103(5):1647-52
references.pmid: 14630823
references.citation: J Biomed Sci. 2011 Aug 19;18:59
references.pmid: 21854621
references.citation: Tissue Eng Part A. 2009 Apr;15(4):869-75
references.pmid: 19191518
references.citation: J Endocrinol. 1999 Feb;160(2):257-66
references.pmid: 9924195
references.citation: Macromol Biosci. 2011 Nov 10;11(11):1458-66
references.pmid: 21994074
references.citation: J Biomed Sci. 2009 Aug 20;16:74
references.pmid: 19691857
references.citation: Exp Cell Res. 2003 Jul 1;287(1):98-105
references.pmid: 12799186
references.citation: FEBS Lett. 2004 Nov 5;577(1-2):277-83
references.pmid: 15527799
references.citation: Int J Biol Sci. 2010 Sep 09;6(5):499-512
references.pmid: 20877435