Kim Ki Joo, Joe Young Ae, Kim Min Kyoung, Lee Su Jin, Ryu Yeon Hee, Cho Dong-Woo, Rhie Jong Won
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.
Cancer Research Institute and Department of Medical Lifescience, The Catholic University of Korea, Seoul, Republic of Korea.
Int J Nanomedicine. 2015 Mar 24;10:2261-72. doi: 10.2147/IJN.S71925. eCollection 2015.
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.
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.
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.
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.
已发现二氧化硅复合材料可增强支架的机械性能，并在体外和体内支持人脂肪组织来源干细胞（hADSCs）的生长。二氧化硅（仅二氧化硅）悬浮于培养基中时以不同大小的颗粒形式存在，但尚不清楚颗粒大小是否会影响二氧化硅对hADSCs的有益作用。在本研究中，我们检测了不同大小颗粒对hADSCs生长和丝裂原活化蛋白激酶信号传导的影响。
通过盐酸和硅酸钠的化学反应制备硅胶，洗涤、灭菌后悬浮于无血清培养基中48小时，然后依次通过0.22μm滤器过滤（滤液中含有小于220nm的纳米颗粒；二氧化硅纳米颗粒）。将hADSCs与二氧化硅纳米颗粒或3μm二氧化硅微粒（MPs）一起孵育，通过透射电子显微镜检查，并检测细胞增殖、凋亡和丝裂原活化蛋白激酶信号传导。
89%的二氧化硅纳米颗粒大小约为50-120nm。当用研究颗粒处理hADSCs时，在hADSCs细胞质内吞泡中观察到二氧化硅纳米颗粒，但二氧化硅微粒未进入细胞。二氧化硅纳米颗粒增加了hADSCs的增殖，但二氧化硅微粒在这方面无显著作用。相反，二氧化硅微粒诱导了轻微凋亡。二氧化硅纳米颗粒增加了细胞外信号调节激酶（ERK）1/2的磷酸化，而二氧化硅微粒增加了p38的磷酸化。二氧化硅纳米颗粒对Janus激酶或p38的磷酸化无影响。用MEK抑制剂PD98059预处理可阻止二氧化硅纳米颗粒诱导的ERK1/2磷酸化和增殖。
用于组织工程的含二氧化硅支架可能仅在包含大小约为50-120nm的纳米颗粒时通过ERK1/2激活来增强细胞生长，且单一组分的二氧化硅衍生纳米颗粒可能对干细胞治疗中的生物支架有用。
