Li Qiang, Han Sei-Myoung, Song Woo-Jin, Park Sang-Chul, Ryu Min-Ok, Youn Hwa-Young
Department of Veterinary Internal Medicine, College of Veterinary Medicine, Seoul National University, Seoul, Republic of Korea.
Department of Veterinary Internal Medicine, College of Veterinary Medicine, Seoul National University, Seoul, Republic of Korea
In Vivo. 2017 May-Jun;31(3):349-356. doi: 10.21873/invivo.11066.
BACKGROUND/AIM: The transcription factors Oct4 and Sox2 enhance the proliferation and pluripotency of human adipose tissue-derived mesenchymal stem cells (hAT-MSCs); however, the anti-inflammatory effects of Oct4- and Sox2-overexpressing hAT-MSCs (Oct4/Sox2-hAT-MSCs) are unclear. Here, we evaluated the anti-inflammatory effects of Oct4/Sox2-hAT-MSCs in vitro and in vivo.
Supernatants from green-fluorescent protein (GFP)- and Oct4/Sox2-hAT-MSCs were used to treat lipopolysaccharide (LPS)-stimulated RAW264.7 cells and inflammatory cytokine expression was determined. In LPS-induced mice, GFP- and Oct4/Sox2-hAT-MSCs were injected intraperitoneally and survival rates, as well as sickness scores of mice, were monitored.
Decreased expression of pro-inflammatory cytokines was observed in Oct4/Sox2-hAT-MSC supernatant-exposed RAW264.7 cells compared to that in GFP-hAT-MSC supernatant-exposed RAW264.7 cells. The sickness score was reduced to 34.9% and the survival rate was increased by 11.1% in Oct4/Sox2-hAT-MSC-injected mice compared to that in GFP-hAT-MSC-injected mice.
Our findings provide important insights into the development of therapies utilizing Oct4/Sox2-hAT-MSCs in inflammatory diseases.
背景/目的：转录因子Oct4和Sox2可增强人脂肪组织来源间充质干细胞（hAT-MSCs）的增殖能力和多能性；然而，过表达Oct4和Sox2的hAT-MSCs（Oct4/Sox2-hAT-MSCs）的抗炎作用尚不清楚。在此，我们评估了Oct4/Sox2-hAT-MSCs在体外和体内的抗炎作用。
用绿色荧光蛋白（GFP）-和Oct4/Sox2-hAT-MSCs的上清液处理脂多糖（LPS）刺激的RAW264.7细胞，并测定炎症细胞因子的表达。在LPS诱导的小鼠中，腹腔注射GFP-和Oct4/Sox2-hAT-MSCs，监测小鼠的存活率和疾病评分。
与暴露于GFP-hAT-MSC上清液的RAW264.7细胞相比，暴露于Oct4/Sox2-hAT-MSC上清液的RAW264.7细胞中促炎细胞因子的表达降低。与注射GFP-hAT-MSCs的小鼠相比，注射Oct4/Sox2-hAT-MSCs的小鼠疾病评分降低至34.9%，存活率提高了11.1%。
我们的研究结果为利用Oct4/Sox2-hAT-MSCs治疗炎症性疾病的疗法开发提供了重要见解
