Ely and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, Center for Reproductive Sciences, Department of Obstetrics, Gynecology and Reproductive Sciences, University of California-San Francisco, CA 94143, USA.
Semin Reprod Med. 2013 Jan;31(1):56-61. doi: 10.1055/s-0032-1331798. Epub 2013 Jan 17.
In humans, very little is known about the factors that regulate trophoblast (TB) specification, expansion of the initial TB population, and formation of the cytotrophoblast (CTB) populations that populate the chorionic villi. The absence of human trophoblast progenitor cell (hTPC) lines that can be propagated in vitro has been a limiting factor. Because attempts to derive TB stem cells from the trophectoderm of the human blastocyst have so far failed, investigators use alternative systems as cell culture models including TBs derived from human embryonic stem cells (hESCs), immortalized CTBs, and cell lines established from TB tumors. Additionally, the characteristics of mature TBs have been extensively studied using primary cultures of CTBs and explants of placental chorionic villi. However, none of these models can be used to study TB progenitor self-renewal and differentiation. Furthermore, the propagation of human TB progenitors from villous CTBs (vCTBs) has not been achieved. The downregulation of key markers of cell cycle progression in vCTBs by the end of the first trimester of pregnancy may indicate that these cells are not a source of human TB progenitors later in pregnancy. In contrast, mesenchymal cells of the villi and chorion continue to proliferate until the end of pregnancy. We recently reported isolation of continuously self-renewing hTPCs from chorionic mesenchyme and showed that they differentiated into the mature TB cell types of the villi, evidence that they can function as TB progenitors. This new cell culture model enables a molecular analysis of the seminal steps in human TB differentiation that have yet to be studied in humans. In turn, this information can be used to trace the origins of pregnancy complications that are associated with faulty TB growth and differentiation.
在人类中，关于调节滋养层（TB）特化、初始 TB 群体扩张以及形成充满绒毛膜绒毛的细胞滋养层（CTB）群体的因素知之甚少。缺乏可在体外增殖的人类滋养层祖细胞（hTPC）系一直是一个限制因素。由于迄今为止从人类胚胎囊胚的滋养外胚层中未能获得 TB 干细胞，因此研究人员使用替代系统作为细胞培养模型，包括源自人类胚胎干细胞（hESC）的 TB、永生化 CTB 和源自 TB 肿瘤的细胞系。此外，还通过 CTB 的原代培养物和胎盘绒毛绒毛的外植体广泛研究了成熟 TB 的特征。然而，这些模型都不能用于研究 TB 祖细胞的自我更新和分化。此外，尚未从绒毛 CTB（vCTB）中扩增人类 TB 祖细胞。妊娠第一期末 vCTB 中细胞周期进程关键标志物的下调可能表明这些细胞不是妊娠后期人类 TB 祖细胞的来源。相比之下，绒毛和绒毛膜的间质细胞会继续增殖直至妊娠末期。我们最近报道了从绒毛间质中分离出持续自我更新的 hTPC，并表明它们分化为绒毛的成熟 TB 细胞类型，这表明它们可以作为 TB 祖细胞发挥作用。这种新的细胞培养模型能够对人类 TB 分化中的关键步骤进行分子分析，这些步骤在人类中尚未研究过。反过来，这些信息可用于追踪与 TB 生长和分化异常相关的妊娠并发症的起源。
