hESCs/hiPSCs体外诱导产生红细胞的研究进展及其临床应用的展望  

Generation of Functionally Mature Erythrocytes From Human Pluripotent Stem Cells:A Review on Methodology

作　　者：毛斌 马峰 

机构地区：[1]中国医学科学院输血研究所干细胞研究中心,成都610052

出　　处：《中国细胞生物学学报》2012年第11期1067-1079,共13页Chinese Journal of Cell Biology

基　　金：国家自然科学基金面上项目(No.81170466/H0801);国家高技术研究发展计划(863计划)(No.2011AA020114)资助项目~~

摘　　要：人类胚胎干细胞和多功能诱导性干细胞的诞生,标志着干细胞研究已经跨入了全新的应用时代。干细胞研究领域的一个重要方向是特定谱系成熟细胞的定向诱导分化。在诸多的血细胞中,成熟红细胞因为无核而携带着最小量的遗传物质,可能作为最早的干细胞治疗产品而应用于输血替代治疗。最近,干细胞向造血细胞(包括红细胞)的研究正方兴未艾。但由于方法学上的偏差,诱导产生的红细胞的成熟度各有所不同。该文在结合了作者实验室的工作经验的基础上,对目前人类多潜能干细胞向红细胞特定诱导分化的方法做了综合的描述,并提出了该研究领域亟需解决的重大科学问题。The knowledge about the early development in human ontogeny has been greatly expanded by the establishment of human embryonic stem cell （hESC） lines and, recently, induced pluripotent stem cells （hiPSC）. In the past decade, hESCs and hiPSCs have been proved good tools in characterization of molecular and cellular mechanisms controlling the normal and diseased differentiation of hematopoietic progenitors and mature, functional blood cells. Most of the types of hematopoietic cells （HCs） derived from hESCs have recently beenshown with functionally mature properties, including erythrocytes, neutrophils, platelets, megakaryocytes, eosinophils, mono- cytes, dendritic cells （DC）, nature killer （NK） cells, mast ceils （MCs） and B/T-lineage lymphoid cells. Along with the advances in research, a clinical translation of hESC/hiPSC-derived HCs as novel therapies has been foreseen in near future. However, different efficiencies in blood cell production have been reported when using different culture systems. We recently established efficient blood cell-inducing systems by co-culture of hESC/hiPSCs with murine fetal stromal cells. In our culture system, hESC/hiPSC-derived hematopoietic progenitors are further induced along to a specific blood cell lineage, such as erythrocytes, MCs and eosinophils, etc. We gained large quantity of purified erythrocytes with maturity and function. In this review, we illustrate the co-culture methods developed in our labo- ratory, along with many different methods developed by other groups, and the technique to induce hESC/hiPSCs to hematopoietic cells and mature erythrocytes. The direction and the problems urgently needing a breakthrough in future research are also addressed.

关 键 词：hESCs hiPSCs 红细胞 原始造血 成体造血 

分 类 号：R329[医药卫生—人体解剖和组织胚胎学]