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一株对紫杉醇耐药并自发向成骨样细胞分化的间充质基质细胞系。

A mesenchymal stromal cell line resistant to paclitaxel that spontaneously differentiates into osteoblast-like cells.

机构信息

Department of Public Health–Microbiology–Virology, University of Milan, Via Pascal 36, 20133, Milan, Italy.

出版信息

Cell Biol Toxicol. 2011 Jun;27(3):169-80. doi: 10.1007/s10565-010-9179-x. Epub 2010 Dec 29.


DOI:10.1007/s10565-010-9179-x
PMID:21190129
Abstract

The mesenchymal stromal cell line SR-4987 has been established in our laboratory from the bone marrow of BDF/1 mice. Recent information on mesenchymal stem cells biology and the need to deal with well-characterized cell lines suggest to critically consider the existent data on this cell line by updating them with new investigations on growth parameters, in vitro plasticity, and drug sensitivity to anti-cancer, anti-inflammatory, and a histone deacetylase inhibitor. SR-4987 cells show a population doubling time of 24.5 ± 5.4 h, a plating efficiency of 2.87 ± 1.19%, and under stimulation maintain only in part their multipotency by differentiating towards chondro-osteogenic lineages but not into adipogenic. Surprisingly, these mesenchymal stromal cells differentiate spontaneously into osteoblast-like cells and this is significantly stimulated by valproic acid. SR-4987 cells show a dramatic resistance to paclitaxel (PTX) with a resistance index of 39.6 times (evaluated versus MOLT-4 leukemia) and of 68.2 (versus HT-29 colorectal carcinoma). SR-4987 resistance is reversed by verapamil and correlates with high expression of P-glycoprotein that is down-modulated by PTX. Taken together, our results indicated that SR-4987 line is a very interesting cell model useful to investigate both drug sensitivity resistance and physiopathological aspects related to mesenchymal cell function.

摘要

我们实验室从 BDF/1 小鼠的骨髓中建立了间充质基质细胞系 SR-4987。最近关于间充质干细胞生物学的信息以及需要处理特征良好的细胞系,建议通过用新的关于生长参数、体外可塑性和对抗癌、抗炎和组蛋白去乙酰化酶抑制剂的药物敏感性的研究来更新这些数据,从而对该细胞系进行批判性的考虑。SR-4987 细胞的倍增时间为 24.5±5.4 小时,接种效率为 2.87±1.19%,在刺激下仅部分维持其多能性,向软骨骨谱系分化,但不向脂肪谱系分化。令人惊讶的是,这些间充质基质细胞自发分化为成骨样细胞,而丙戊酸能显著刺激这种分化。SR-4987 细胞对紫杉醇(PTX)表现出明显的耐药性,耐药指数为 39.6 倍(与 MOLT-4 白血病相比)和 68.2 倍(与 HT-29 结直肠癌细胞相比)。维拉帕米可逆转 SR-4987 的耐药性,与 P-糖蛋白的高表达相关,而 P-糖蛋白被 PTX 下调。综上所述,我们的结果表明,SR-4987 系是一种非常有趣的细胞模型,可用于研究药物敏感性耐药性和与间充质细胞功能相关的生理病理方面。

相似文献

[1]
A mesenchymal stromal cell line resistant to paclitaxel that spontaneously differentiates into osteoblast-like cells.

Cell Biol Toxicol. 2010-12-29

[2]
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引用本文的文献

[1]
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Am J Transl Res. 2017-6-15

[2]
Human mesenchymal stromal cells inhibit tumor growth in orthotopic glioblastoma xenografts.

Stem Cell Res Ther. 2017-3-9

[3]
Mesenchymal stromal cells loaded with paclitaxel induce cytotoxic damage in glioblastoma brain xenografts.

Stem Cell Res Ther. 2015-10-6

[4]
Drug-releasing mesenchymal cells strongly suppress B16 lung metastasis in a syngeneic murine model.

J Exp Clin Cancer Res. 2015-8-13

[5]
Mesenchymal stromal cells primed with paclitaxel provide a new approach for cancer therapy.

PLoS One. 2011-12-20

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