The "Compass to Healthy Life" Research Complex Program, RIKEN Institute, Kobe, 650-0047, Japan.
Research Promotion Institution for COI Site, Kyoto University, Kyoto, Japan.
Stem Cell Res Ther. 2019 Aug 7;10(1):245. doi: 10.1186/s13287-019-1339-1.
Trophoblasts as a specific cell lineage are crucial for the correct function of the placenta. Human trophoblast stem cells (hTSCs) are a proliferative population that can differentiate into syncytiotrophoblasts and extravillous cytotrophoblasts. Many studies have reported that chemical supplements induce the differentiation of trophoblasts from human induced pluripotent stem cells (hiPSCs). However, there have been no reports of the establishment of proliferative hTSCs from hiPSCs. Our previous report showed that culturing hiPSCs on micromesh as a bioscaffold induced cystic cells with trophoblast properties. Here, we aimed to establish hTSCs from hiPSCs.
We used the micromesh culture technique to induce hiPSC differentiation into trophoblast cysts. We then reseeded and purified cystic cells.
The cells derived from the reseeded cysts were highly proliferative. Low expression levels of pluripotency genes and high expression levels of TSC-specific genes were detected in proliferative cells. The cells could be passaged, and further directional differentiation into syncytiotrophoblast- and extravillous cytotrophoblast-like cells was confirmed by marker expression and hormone secretion.
We established hiPSC-derived hTSCs, which may be applicable for studying the functions of trophoblasts and the placenta. Our experimental system may provide useful tools for understanding the pathogenesis of infertility owing to trophoblast defects in the future.
滋养层作为一种特定的细胞谱系，对胎盘的正常功能至关重要。人滋养层干细胞（hTSC）是一种增殖性细胞群，可分化为合体滋养层细胞和细胞滋养层细胞。许多研究报道，化学补充剂可诱导人诱导多能干细胞（hiPSC）分化为滋养层细胞。然而，尚未有从 hiPSC 中建立增殖性 hTSC 的报道。我们之前的报告表明，将 hiPSC 培养在微网作为生物支架上可诱导具有滋养层特性的囊状细胞。在此，我们旨在从 hiPSC 中建立 hTSC。
我们使用微网培养技术诱导 hiPSC 分化为滋养层囊。然后我们重新接种和纯化囊状细胞。
重新接种的囊中的细胞具有高度的增殖能力。在增殖细胞中检测到多能性基因的低表达水平和 TSC 特异性基因的高表达水平。这些细胞可传代，并且通过标志物表达和激素分泌进一步证实其可定向分化为合体滋养层细胞和细胞滋养层细胞样细胞。
我们建立了 hiPSC 来源的 hTSC，这可能适用于研究滋养层和胎盘的功能。我们的实验系统将来可能为理解由于滋养层缺陷导致的不孕的发病机制提供有用的工具。
