人胚胎干细胞诱导分化的肝样细胞质量评价研究  

A discussion on the quality evaluation practice of human embryonic stem cells-derived hepatocyte-like cells

作　　者：纳涛[1] 孙懿[2,3] 吴婷婷 欧阳琦 卢光琇[2,3] 林戈 袁宝珠[1] NA Tao;SUN Yi;WU Ting-ting;OUYANG Qi;LU Guang-xiu;LIN Ge;YUAN Bao-zhu(The Cell Collection and Research Center,National Institutes for Food and Drug Control,Key Laboratory of the Ministry of Health for Research on Quality and Standardization of Biotech Products,Beijing 100050,China;National Engineering and Research Center of Human Stem Cells,Changsha 410205,China;Hunan Guangxiu GaoXin Life Science Co.,Ltd.,Changsha 410205,China)

机构地区：[1]中国食品药品检定研究院,细胞资源保藏研究中心,卫生部生物技术产品检定方法及其标准化重点实验室,北京100050 [2]人类干细胞国家工程研究中心,长沙410205 [3]湖南光琇高新生命科技有限公司,长沙410205

出　　处：《中国新药杂志》2021年第4期320-332,共13页Chinese Journal of New Drugs

摘　　要：肝细胞、肝组织或器官移植是目前不可逆失代偿性肝病的主要治疗手段,而由人胚胎干细胞诱导分化来源的肝样细胞(human embryonic stem cells-derived hepatocyte-like cells,h ESC-HLCs)能为移植提供数量充足、质量可控、来源稳定的细胞。为满足临床应用研究的需要,hESC-HLCs需具备明确的基本生物学属性、微生物学安全性、生物学安全性及生物学有效性的总体质量要求,其中每一类质量要求是由多个关键质量属性所组成。hESC-HLCs的整个制备过程是从人胚胎干细胞(hESCs)向hESC-HLCs的全分化过程,可基本分为4个阶段,各阶段在细胞形态、标志基因/蛋白的表达、生物学功能等方面均有明显的特征。本文就h ESC-HLCs总体质量要求及各质量属性进行讨论,目的是在我国建立临床研究用hESC-HLCs质量评价方法和评价策略。Transplantation with liver cells,tissue or organ remains the first-line treatment for terminal irreversible liver failure. Human embryonic stem cells-derived hepatocyte-like cells( hESC-HLCs) may represent a stable,effective and well-controlled cell source for the transplantation. To meet the quality requirements for clinical use,hESC-HLCs must possess four major quality attributes,i. e. general biological attributes,microbiology safety,biological safety and biological effectiveness,with each category comprising of a number of key quality attributes.The manufacturing process of hESC-HLCs starting from hESCs and ending with the completion of hESC-HLCs differentiation can be divided into four relatively distinct stages with each stage featured with relatively specific cell morphology,biomarkers,biological activities,and so on. In this report,we provided a comprehensive discussion on the quality requirements and key quality attributes of h ESC-HLCs with the goal of establishment of a quality evaluation system and development of relevant evaluation strategies for ensuring both safety and effectiveness of h ESC-HLCs to be used in clinical studies.

关 键 词：胚胎干细胞 肝样细胞 质量属性 质量评价 阶段性诱导分化 

分 类 号：R96[医药卫生—药理学]