PMID- 25848249 OWN - NLM STAT- MEDLINE DCOM- 20161028 LR - 20181202 IS - 1178-2013 (Electronic) IS - 1176-9114 (Print) IS - 1176-9114 (Linking) VI - 10 DP - 2015 TI - Silica nanoparticles increase human adipose tissue-derived stem cell proliferation through ERK1/2 activation. PG - 2261-72 LID - 10.2147/IJN.S71925 [doi] AB - 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 mum filter (filtrate containing nanoparticles smaller than 220 nm; silica NPs). hADSCs were incubated with silica NPs or 3 mum 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. CONCLUSION: 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. FAU - Kim, Ki Joo AU - Kim KJ AD - 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. FAU - Joe, Young Ae AU - Joe YA AD - Cancer Research Institute and Department of Medical Lifescience, The Catholic University of Korea, Seoul, Republic of Korea. FAU - Kim, Min Kyoung AU - Kim MK AD - 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. FAU - Lee, Su Jin AU - Lee SJ AD - Department of Plastic Surgery, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea. FAU - Ryu, Yeon Hee AU - Ryu YH AD - 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. FAU - Cho, Dong-Woo AU - Cho DW AD - 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. FAU - Rhie, Jong Won AU - Rhie JW AD - 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. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150324 PL - New Zealand TA - Int J Nanomedicine JT - International journal of nanomedicine JID - 101263847 RN - 0 (Flavonoids) RN - 7631-86-9 (Silicon Dioxide) RN - EC 2.7.11.24 (MAPK1 protein, human) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3) RN - SJE1IO5E3I (2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one) SB - IM MH - Adipose Tissue/*cytology MH - Apoptosis/drug effects MH - Cell Proliferation/drug effects MH - Cells, Cultured MH - Flavonoids/pharmacology MH - Humans MH - MAP Kinase Signaling System MH - Microscopy, Electron, Transmission MH - Mitogen-Activated Protein Kinase 1/*metabolism MH - Mitogen-Activated Protein Kinase 3/metabolism MH - *Nanoparticles/chemistry MH - Particle Size MH - Phosphorylation MH - Signal Transduction/drug effects MH - Silicon Dioxide/*chemistry/pharmacology MH - Stem Cells/*cytology/drug effects/physiology MH - Tissue Scaffolds PMC - PMC4378289 OTO - NOTNLM OT - ERK OT - biomaterial OT - ceramic OT - mesenchymal stem cells OT - particle EDAT- 2015/04/08 06:00 MHDA- 2016/11/01 06:00 PMCR- 2015/03/24 CRDT- 2015/04/08 06:00 PHST- 2015/04/08 06:00 [entrez] PHST- 2015/04/08 06:00 [pubmed] PHST- 2016/11/01 06:00 [medline] PHST- 2015/03/24 00:00 [pmc-release] AID - ijn-10-2261 [pii] AID - 10.2147/IJN.S71925 [doi] PST - epublish SO - Int J Nanomedicine. 2015 Mar 24;10:2261-72. doi: 10.2147/IJN.S71925. eCollection 2015.