• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Biotechnology Progress >Testing the Potency of Anti-TNF-alpha and Anti-IL-1 beta Drugs Using Spheroid Cultures of Human Osteoarthritic Chondrocytes and Donor-Matched Chondrogenically Differentiated Mesenchymal Stem Cells
【24h】

Testing the Potency of Anti-TNF-alpha and Anti-IL-1 beta Drugs Using Spheroid Cultures of Human Osteoarthritic Chondrocytes and Donor-Matched Chondrogenically Differentiated Mesenchymal Stem Cells

机译：使用人骨关节炎软骨细胞的球状培养物和供体匹配的软弱性分化间充质干细胞来测试抗TNF-α和抗IL-1β药物的效力

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Inflammation plays a major role in progression of rheumatoid arthritis, a disease treated with antagonists of tumor necrosis factor-alpha (TNF-alpha) and interleukin 1 beta (IL-1 beta). New in vitro testing systems are needed to evaluate efficacies of new anti-inflammatory biological drugs, ideally in a patient-specific manner. To address this need, we studied microspheroids containing 10,000 human osteoarthritic primary chondrocytes (OACs) or chondrogenically differentiated mesenchymal stem cells (MSCs), obtained from three donors. Hypothesizing that this system can recapitulate clinically observed effects of anti-inflammatory drugs, spheroids were exposed to TNF-alpha, IL-1 beta, or to supernatant containing secretome from activated macrophages (MCM). The anti-inflammatory efficacies of anti-TNF-alpha biologicals adalimumab, infliximab, and etanercept, and the anti-IL-1 beta agent anakinra were assessed in short-term microspheroid and long-term macrospheroid cultures (100,000 OACs). While gene and protein expressions were evaluated in microspheroids, diameters, amounts of DNA, glycosaminoglycans, and hydroxiproline were measured in macrospheroids. The tested drugs significantly decreased the inflammation induced by TNF-alpha or IL-1 beta. The differences in potency of anti-TNF-alpha biologicals at 24 h and 3 weeks after their addition to inflamed spheroids were comparable, showing high predictability of short-term cultures. Moreover, the data obtained with microspheroids grown from OACs and chondrogenically differentiated MSCs were comparable, suggesting that MSCs could be used for this type of in vitro testing. We propose that in vitro gene expression measured after the first 24 h in cultures of chondrogenically differentiated MSCs can be used to determine the functionality of anti-TNF-alpha drugs in personalized and preclinical studies. (C) 2018 American Institute of Chemical Engineers
机译：炎症在类风湿性关节炎的进展中发挥着重要作用，该疾病与肿瘤坏死因子-α（TNF-α）和白细胞介素1β（IL-1β）的拮抗剂治疗。需要新的体外测试系统来评估新的抗炎生物药物的疗效，理想地以患者特异性方式。为了满足这种需求，我们研究了从三种供体中获得的含有10,000个人骨关节炎初级软骨细胞（OAC）或软弱化分化的间充质干细胞（MSC）的微球体。假设该系统可以重新承载临床观察到的抗炎药的影响，球状体暴露于TNF-α，IL-1β，或通过活化的巨噬细胞（MCM）含有秘酐的上清液。在短期微球体和长期宏观体培养物（100,000个OAC）中评估抗TNF-α生物杀螨氨酸，英夫利昔单抗和依赖达替替替替替替替替替替尼单抗和抗IL-1β代理Anakina的抗炎效率。虽然在微球体中评价基因和蛋白质表达，但在宏观体中测量直径，DNA，糖胺聚糖和羟丙啉。测试的药物显着降低TNF-α或IL-1β诱导的炎症。抗TNF-α生物学效力效力在24小时和3周内与发炎的球状体24小时相当，显示出短期培养的高可预测性。此外，通过从OAC生长和软弱化学分化的MSCs生长的微球体获得的数据具有可比性，表明MSC可用于这种类型的体外测试。我们提出在软骨外分化的MSCs培养物中的前24小时后测量的体外基因表达可用于确定个性化和临床前研究的抗TNF-α药物的功能。 （c）2018美国化学工程研究所

著录项

相似文献

  • 外文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号