Distinct adipogenic differentiation phenotypes of human umbilical cord mesenchymal cells dependent on adipogenic conditions.
Distinct adipogenic differentiation phenotypes of human umbilical cord mesenchymal cells dependent on adipogenic conditions.
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人脐带间充质细胞的独特脂肪生成分化表型取决于成脂条件。
DOI：
10.1177/1535370214539225
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发表时间：
2014-10
期刊：
影响因子：
--
通讯作者：
Shankar K
中科院分区：
文献类型：
--
作者：
Saben J;Thakali KM;Lindsey FE;Zhong Y;Badger TM;Andres A;Shankar K
脐带（UC）基质是多能间充质干细胞（MSC）的来源，具有脂肪形成潜力，因此可以作为研究脂肪形成的模型。然而，脂肪细胞分化结果存在的差异可能是由于脂肪形成分化所用方法的差异所致。此外，UCMSC 作为脂肪细胞的功能特征尚未描述。我们测试了三种成熟的脂肪形成混合物（含有 IBMX、地塞米松和胰岛素 (MDI) 加吲哚美辛 (MDI-I) 或罗格列酮 (MDI-R)）刺激 UCMSC 脂肪细胞分化的潜力。 MDI、MDI-I 和 MDI-R 处理显着增加 PPARγ 和 C/EBPα mRNA 并诱导脂滴形成。然而，MDI-I对PPARγ、C/EBPα、FABP4、GPD1、PLIN1、PLIN2和ADIPOQ的mRNA表达以及脂质积累的影响最大，而MDI的影响最小。有趣的是，治疗组的 PPARγ 蛋白含量没有差异。然而，与 MDI 或 MDI-R 相比，MDI-I 处理的细胞具有显着更多的 C/EBPα 蛋白，表明吲哚美辛依赖性增加的 C/EBPα 可能有助于 MDI-I 的脂肪生成诱导效力。此外，BMP4 处理 UC-MSC 并没有增强对 MDI 诱导分化的反应。最后，为了表征脂肪细胞功能，用胰岛素刺激分化的 UCMSC，并评估下游信号传导。分化的UCMSCs在两周时对胰岛素有反应，但在分化后五周时敏感性下降，表明长期分化可能诱发胰岛素抵抗。总之，这些数据表明，UCMSCs 在 MDI、MDI-I、MDI-R 中分化时经历脂肪形成，然而吲哚美辛的存在大大增强了它们的脂肪形成潜力，超过了罗格列酮。此外，我们的结果表明分化的 UCMSC 的胰岛素信号通路在功能上与脂肪细胞相似。
The umbilical cord (UC) matrix is a source of multipotent mesenchymal stem cells (MSCs) that have adipogenic potential and thus can be a model to study adipogenesis. However, existing variability in adipocytic differentiation outcomes may be due to discrepancies in methods utilized for adipogenic differentiation. Additionally, functional characterization of UCMSCs as adipocytes has not been described. We tested the potential of three well-established adipogenic cocktails containing IBMX, dexamethasone, and insulin (MDI) plus indomethacin (MDI-I) or rosiglitazone (MDI-R) to stimulate adipocyte differentiation in UCMSCs. MDI, MDI-I, and MDI-R treatment significantly increased PPARγ and C/EBPα mRNA and induced lipid droplet formation. However, MDI-I had the greatest impact on mRNA expressions of PPARγ, C/EBPα, FABP4, GPD1, PLIN1, PLIN2, and ADIPOQ and lipid accumulation, whereas MDI showed the least. Interestingly, there were no treatment group differences in the amount of PPARγ protein. However, MDI-I treated cells had significantly more C/EBPα protein compared to MDI or MDI-R, suggesting that indomethacin-dependent increased C/EBPα may contribute to the adipogenesis-inducing potency of MDI-I. Additionally, BMP4 treatment of UC-MSCs did not enhance responsiveness to MDI-induced differentiation. Finally to characterize adipocyte function, differentiated UCMSCs were stimulated with insulin and downstream signaling was assessed. Differentiated UCMSCs were responsive to insulin at two weeks but showed decreased sensitivity by five weeks following differentiation, suggesting that long-term differentiation may induce insulin resistance. Together, these data indicate that UCMSCs undergo adipogenesis when differentiated in MDI, MDI-I, MDI-R, however the presence of indomethacin greatly enhances their adipogenic potential beyond that of rosiglitazone. Furthermore, our results suggest that insulin signaling pathways of differentiated UCMSCs are functionally similar to adipocytes.
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影响因子：
5.6
作者：
Kim DW;Staples M;Shinozuka K;Pantcheva P;Kang SD;Borlongan CV
通讯作者：
Borlongan CV
影响因子：
5.4
作者：
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DOI：
10.1073/pnas.1211255110
发表时间：
2013-02-12
影响因子：
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作者：
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通讯作者：
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DOI：
10.1016/j.bbrc.2011.09.001
发表时间：
2011-10-07
影响因子：
3.1
作者：
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通讯作者：
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影响因子：
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作者：
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