Varberg Kaela M, Moreno-Irusta Ayelen, Novoa Allynson, Musser Brynne, Varberg Joseph M, Goering Jeremy P, Saadi Irfan, Iqbal Khursheed, Okae Hiroaki, Arima Takahiro, Williams John, Pisarska Margareta D, Soares Michael J
1nstitute for Reproductive and Developmental Sciences, Department of Pathology & Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS 66160.
Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center, Los Angeles, CA.
medRxiv. 2024 Jul 23:2022.12.07.22283218. doi: 10.1101/2022.12.07.22283218.
Human trophoblast stem () cells are an informative in vitro model for the generation and testing of biologically meaningful hypotheses. The goal of this project was to derive patient-specific TS cell lines from clinically available chorionic villus sampling biopsies. Cell outgrowths were captured from human chorionic villus tissue specimens cultured in modified human TS cell medium. Cell colonies emerged early during the culture and cell lines were established and passaged for several generations. Karyotypes of the newly established chorionic villus-derived trophoblast stem ( ) cell lines were determined and compared to initial genetic diagnoses from freshly isolated chorionic villi. Phenotypes of TS cells in the stem state and following differentiation were compared to cytotrophoblast-derived TS ( ) cells. TS and TS cells uniformly exhibited similarities in the stem state and following differentiation into syncytiotrophoblast and extravillous trophoblast cells. Chorionic villus tissue specimens provide a valuable source for TS cell derivation. They expand the genetic diversity of available TS cells and are associated with defined clinical outcomes. TS cell lines provide a new set of experimental tools for investigating trophoblast cell lineage development.
人滋养层干细胞(TS细胞)是用于生成和检验具有生物学意义的假说的一种信息丰富的体外模型。本项目的目标是从临床可用的绒毛取样活检中获得患者特异性TS细胞系。从在改良的人TS细胞培养基中培养的人绒毛组织标本中获取细胞生长物。细胞集落于培养早期出现,并建立细胞系并传代培养数代。确定新建立的绒毛膜绒毛来源的滋养层干细胞(TS细胞)系的核型,并与新鲜分离的绒毛膜绒毛的初始基因诊断结果进行比较。将处于干细胞状态及分化后的TS细胞的表型与细胞滋养层来源的TS细胞进行比较。TS细胞和TS细胞在干细胞状态以及分化为合体滋养层细胞和绒毛外滋养层细胞后均表现出相似性。绒毛膜绒毛组织标本为TS细胞的衍生提供了宝贵来源。它们扩展了现有TS细胞的遗传多样性,并与明确的临床结果相关。TS细胞系为研究滋养层细胞谱系发育提供了一套新的实验工具。