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软骨细胞基因表达受长期体外 MRI 跟踪中铁氧化物纳米颗粒标记的影响。

Chondrocyte gene expression is affected by very small iron oxide particles-labeling in long-term in vitro MRI tracking.

机构信息

Orthopedic Research Laboratory, Aarhus University Hospital, NBG, Aarhus, Denmark.

出版信息

J Magn Reson Imaging. 2011 Mar;33(3):724-30. doi: 10.1002/jmri.22470.

DOI:10.1002/jmri.22470
PMID:21563258
Abstract

PURPOSE

To investigate the effect and dose response of very small iron oxide particles (VSOP) labeling of human chondrocytes for long-term in vitro MRI tracking.

MATERIALS AND METHODS

Chondrocytes were isolated from cartilage biopsies from four patients. The cells for the dose-response study were labeled with 25, 50, or 100 μg/mL VSOP. Quantitative gene expression and cellular proliferation were compared with unlabeled controls at day 1, 3, and 7. The cells suited for MRI tracking were labeled with 50 μg/mL VSOP and embedded in alginate beads, followed by MRI (using T2-weighted sequences) at day 0, 1, 3, 7, 14, 21, 28, and histology was performed at each time-point.

RESULTS

Histology revealed that VSOP particles were intracellularly confined at all time-points, whereas no extracellular VSOPs were observed. A mean reduction in T2-value of 25.1 ms (±SD 3.5 ms) was found on T2-maps. The chondrocyte-specific genes aggrecan, collagen type 2, and sox9 were all affected by labeling, the two latter in a dose-dependent manner. VSOPs had no effect on proliferation.

CONCLUSION

VSOP labeling of chondrocytes affected gene expression but not proliferation. The labeled chondrocytes could be recognized by MRI for 4 weeks without significant changes in the T2 relaxation time.

摘要

目的

研究超小氧化铁颗粒(VSOP)标记人软骨细胞用于长期体外 MRI 跟踪的效果和剂量反应。

材料和方法

从 4 名患者的软骨活检中分离出软骨细胞。用于剂量反应研究的细胞用 25、50 或 100μg/ml VSOP 进行标记。在第 1、3 和 7 天与未标记的对照进行定量基因表达和细胞增殖比较。适合 MRI 跟踪的细胞用 50μg/ml VSOP 标记,并嵌入藻酸盐珠中,然后在第 0、1、3、7、14、21、28 天进行 MRI(使用 T2 加权序列),并在每个时间点进行组织学检查。

结果

组织学显示,VSOP 颗粒在所有时间点都局限于细胞内,而没有观察到细胞外的 VSOP。在 T2 图谱上发现 T2 值平均降低了 25.1ms(±3.5ms)。软骨细胞特异性基因聚集蛋白聚糖、胶原类型 2 和 sox9 均受到标记的影响,后两者呈剂量依赖性。VSOP 对增殖没有影响。

结论

VSOP 标记软骨细胞会影响基因表达,但不会影响增殖。标记的软骨细胞可通过 MRI 识别 4 周,T2 弛豫时间无明显变化。

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