Trophoblast differentiation in embryoid bodies derived from human embryonic stem cells
Trophoblast differentiation in embryoid bodies derived from human embryonic stem cells
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DOI：
10.1210/en.2003-1241
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发表时间：
2004-04-01
期刊：
影响因子：
4.8
通讯作者：
Golos, TG
中科院分区：
文献类型：
--
作者：
Gerami-Naini, B;Dovzhenko, OV;Golos, TG
滋养层分化和早期胎盘发育对于妊娠的建立至关重要，但这些关键事件在人类妊娠中尚不易于研究。我们使用从人胚胎干（hES）细胞制备的拟胚体（EB）作为早期人类发育的体外模型。悬浮培养 1 周的 hES 细胞来源的 EB 培养基中人绒毛膜促性腺激素 (hCG)、黄体酮和雌二醇 17β 的水平高于未条件培养基或来自未分化 hES 细胞或自发分化 hES 细胞集落的培养基。将 EB 移植到 Matrigel (MG)“筏”中并培养长达 53 天。在 MG 三维生长的前 7 - 10 d 中，EB 的外表面出现小突起，其中一些随后延伸成多细胞生长物。 hCG、黄体酮和雌二醇-17β的分泌在 MG 培养的第 20 天左右开始增加，并在接下来的 30 天中保持显着升高。维持悬浮培养的 EB 未能证明激素分泌的这种升高。悬浮培养和 MG 包埋的 EB 表现出细胞角蛋白 7/8 的广泛表达，表明广泛的上皮分化以及一致的 hCG 表达。我们认为 hES 细胞衍生的 EB 可能是研究人类滋养层分化和胎盘形态发生的有用模型。
Trophoblast differentiation and early placental development are essential for the establishment of pregnancy, yet these critical events are not readily investigated in human pregnancy. We used embryoid bodies ( EBs) prepared from human embryonic stem (hES) cells as an in vitro model of earlyhuman development. The levels of human chorionic gonadotropin (hCG), progesterone, and estradiol-17beta in medium from hES cell-derived EBs grown in suspension culture for 1 wk were higher than unconditioned culture medium or medium from undifferentiated hES cells or spontaneously differentiated hES cell colonies. EBs were explanted into Matrigel (MG) "rafts" and cultured for up to 53 d. During the first 7 - 10 d of three-dimensional growth in MG, small protrusions appeared on the outer surface of EBs, some of which subsequently extended into multicellular outgrowths. The secretion of hCG, progesterone, and estradiol-17beta began to increase on approximately d 20 of MG culture and remained dramatically elevated over the next 30 d. EBs maintained in suspension culture failed to demonstrate this elevation in hormone secretion. Suspension-cultured and MG-embedded EBs exhibited widespread expression of cytokeratins 7/8, demonstrating extensive epithelial differentiation as well as consistent hCG expression. We propose that hES cell-derived EBs may be a useful model for investigation of human trophoblast differentiation and placental morphogenesis.