title: Silica nanoparticles increase human adipose tissue-derived stem cell proliferation through ERK1/2 activation.
abstract: BACKGROUND
  Silicon dioxide composites have been found to enhance the mechanical properties of scaffolds and to support growth of human adipose tissue-derived stem cells (hADSCs) both in vitro and in vivo. Silica (silicon dioxide alone) exists as differently sized particles when suspended in culture medium, but it is not clear whether particle size influences the beneficial effect of silicon dioxide on hADSCs. In this study, we examined the effect of different sized particles on growth and mitogen-activated protein kinase signaling in hADSCs.
  
  
  METHODS
  Silica gel was prepared by a chemical reaction using hydrochloric acid and sodium silicate, washed, sterilized, and suspended in serum-free culture medium for 48 hours, and then sequentially filtered through a 0.22 μm filter (filtrate containing nanoparticles smaller than 220 nm; silica NPs). hADSCs were incubated with silica NPs or 3 μm silica microparticles (MPs), examined by transmission electron microscopy, and assayed for cell proliferation, apoptosis, and mitogen-activated protein kinase signaling.
  
  
  RESULTS
  Eighty-nine percent of the silica NPs were around 50-120 nm in size. When hADSCs were treated with the study particles, silica NPs were observed in endocytosed vacuoles in the cytosol of hADSCs, but silica MPs showed no cell entry. Silica NPs increased the proliferation of hADSCs, but silica MPs had no significant effect in this regard. Instead, silica MPs induced slight apoptosis. Silica NPs increased phosphorylation of extracellular signal-related kinase (ERK)1/2, while silica MPs increased phosphorylation of p38. Silica NPs had no effect on phosphorylation of Janus kinase or p38. Pretreatment with PD98059, a MEK inhibitor, prevented the ERK1/2 phosphorylation and proliferation induced by silica NPs.
  
  
  CONCLUSIONS
  Scaffolds containing silicon dioxide for tissue engineering may enhance cell growth through ERK1/2 activation only when NPs around 50-120 nm in size are included, and single component silica-derived NPs could be useful for bioscaffolds in stem cell therapy.
authors.affiliation: Department of Plastic Surgery, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea ; Department of Molecular Biomedicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Ki Joo
authors.initials: KJ
authors.lastname: Kim
authors.affiliation: Cancer Research Institute and Department of Medical Lifescience, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Young Ae
authors.initials: YA
authors.lastname: Joe
authors.affiliation: Department of Plastic Surgery, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea ; Department of Molecular Biomedicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Min Kyoung
authors.initials: MK
authors.lastname: Kim
authors.affiliation: Department of Plastic Surgery, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Su Jin
authors.initials: SJ
authors.lastname: Lee
authors.affiliation: Department of Plastic Surgery, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea ; Department of Molecular Biomedicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Yeon Hee
authors.initials: YH
authors.lastname: Ryu
authors.affiliation: Department of Mechanical Engineering, Pohang University of Science and Technology, Gyeongbuk, Republic of Korea ; Department of Integrative Bioscience and Bioengineering, Pohang University of Science and Technology, Gyeongbuk, Republic of Korea.
authors.forename: Dong-Woo
authors.initials: DW
authors.lastname: Cho
authors.affiliation: Department of Plastic Surgery, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea ; Department of Molecular Biomedicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Jong Won
authors.initials: JW
authors.lastname: Rhie
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D020935:MAP Kinase Signaling System; D046529:Microscopy, Electron, Transmission; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D053758:Nanoparticles / Q000737:chemistry; D010316:Particle Size; D010766:Phosphorylation; D015398:Signal Transduction / Q000187:drug effects; D012822:Silicon Dioxide / Q000737:chemistry* / Q000494:pharmacology; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D054457:Tissue Scaffolds
chemical_list: D005419:Flavonoids; D012822:Silicon Dioxide; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one
keywords: ERK; biomaterial; ceramic; mesenchymal stem cells; particle
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