Development of a human adipocyte model derived from human mesenchymal stem cells (hMSC) as a tool for toxicological studies on the action of TCDD
Development of a human adipocyte model derived from human mesenchymal stem cells (hMSC) as a tool for toxicological studies on the action of TCDD
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DOI：
10.1515/bc.2008.015
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发表时间：
2008-02-01
影响因子：
3.7
通讯作者：
Matsumura, Fumio
中科院分区：
文献类型：
--
作者：
Li, Wen;Vogel, Christoph F. A.;Matsumura, Fumio
努力建立一个人脂肪细胞模型，用于体外毒理学研究。为此，研究人员用胰岛素、地塞米松、吲哚美辛和3-异丁基-1-甲基黄嘌呤处理人类骨髓细胞，诱导干细胞分化为脂肪细胞，然后在仅添加胰岛素的Dulbecco改良Eagle培养基中再孵育3天。在大多数情况下，经过这样一个周期的分化处理后分化的细胞会进一步进行第二个周期的分化。所得到的2周期分化细胞具有许多典型脂肪细胞的特征。二恶英（TCDD）在诱导分化激素鸡尾酒治疗开始时加入，明显阻止了它们成为脂肪细胞，就像用TCDD处理的3T3-L1细胞一样。此外，TCDD，即使给药于先前分化的人间充质干细胞（hMSC）脂肪细胞，在TCDD作用的早期（24小时）持续诱导炎症反应的迹象，随后在5天的孵育期间逐渐失去脂肪细胞特异性标志物。总之，hmsc衍生的脂肪细胞似乎为未来的毒理学研究提供了一个有希望的人类细胞模型。
Efforts were made to develop a human adipocyte model that is useful for toxicological studies in vitro. For this purpose, a stem cell line derived from human bone marrow cells, originally from an adult, was induced to differentiate towards adipocytes by treating them with insulin, dexamethasone, indomethacin and 3-isobutyl-1-methylxanthine for 3 d, followed by additional incubation for 3 d in Dulbecco's modified Eagle's medium supplemented with insulin only. In most cases, thus differentiated cells through such one cycle of differentiation treatment were further subjected to the second cycle of differentiation. The resulting 2-cycle differentiated cells were found to exhibit many characteristics of typical adipocytes. Dioxin (TCDD), when added at the beginning of their treatment with differentiation-inducing hormone cocktail, clearly prevented them from becoming adipocytes, as in the case of TCDD-treated 3T3-L1 cells. Furthermore, TCDD, even when administered to previously differentiated human mesenchymal stem cells (hMSC) adipocytes, consistently induced the sign of inflammatory responses during the early period of TCDD action (24 h), which was followed by gradual loss of adipocyte-specific markers during the 5-d incubation period. In conclusion, hMSC-derived adipocytes appear to offer a promising human cell model suited for future toxicological studies.