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用铟-111标记人间充质干细胞用于单光子发射计算机断层显像(SPECT)成像:对细胞增殖和分化的影响

Labelling of human mesenchymal stem cells with indium-111 for SPECT imaging: effect on cell proliferation and differentiation.

作者信息

Bindslev L, Haack-Sørensen M, Bisgaard K, Kragh L, Mortensen S, Hesse B, Kjaer A, Kastrup J

机构信息

Stem Cell Laboratory 9312, The Heart Centre, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.

出版信息

Eur J Nucl Med Mol Imaging. 2006 Oct;33(10):1171-7. doi: 10.1007/s00259-006-0093-7. Epub 2006 Jun 9.

Abstract

PURPOSE

Stem cell therapy seems to be a new treatment option within cardiac diseases to improve myocardial perfusion and function. However, the delivery and traceability of the cells represent a problem. Radioactive labelling with 111In could be a method for tracking mesenchymal stem cells (MSCs). However, 111In could influence the viability and differentiation capacity of MSCs, which would limit its use. Therefore, the aim of this study was to evaluate the influence of 111In labelling in doses relevant for SPECT imaging in humans on the viability and differentiation capacity of human MSCs.

METHODS AND RESULTS

Human MSCs isolated from bone marrow were incubated with 111In-tropolone (15-800 Bq/cell). The labelling efficiency was approximately 25% with 30 Bq/cell 111In. The MSC doubling time was 1.04+/-0.1 days and was not influenced by 111In within the range 15-260 Bq/cell. Using 30 Bq 111In/cell it was possible to label MSCs to a level relevant for clinical scintigraphic use. With this dose, 111In had no effect on characteristic surface and intracellular markers of cultured MSCs analysed both by flow cytometry and by real-time polymerase chain reaction. Further, the labelled MSCs differentiated towards endothelial cells and formed vascular structures.

CONCLUSION

It is possible to label human MSCs with 111In for scintigraphic tracking of stem cells delivered to the heart in clinical trials without affecting the viability and differentiation capacity of the MSCs. This creates an important tool for the control of stem cell delivery and dose response in clinical cardiovascular trials.

摘要

目的

干细胞疗法似乎是治疗心脏病以改善心肌灌注和功能的一种新选择。然而,细胞的递送和追踪是个问题。用铟 - 111进行放射性标记可能是追踪间充质干细胞(MSC)的一种方法。然而,铟 - 111可能会影响MSC的活力和分化能力,这将限制其应用。因此,本研究的目的是评估与人体单光子发射计算机断层显像(SPECT)成像相关剂量的铟 - 111标记对人MSC活力和分化能力的影响。

方法与结果

从骨髓中分离出的人MSC与铟 - 111 - 托酚酮(15 - 800贝可勒尔/细胞)一起孵育。用30贝可勒尔/细胞的铟 - 111时标记效率约为25%。MSC的倍增时间为1.04±0.1天,在15 - 260贝可勒尔/细胞范围内不受铟 - 111影响。使用30贝可勒尔/细胞的铟 - 111能够将MSC标记到临床闪烁显像适用的水平。在此剂量下,通过流式细胞术和实时聚合酶链反应分析,铟 - 111对培养的MSC的特征性表面和细胞内标志物均无影响。此外,标记的MSC向内皮细胞分化并形成血管结构。

结论

在不影响MSC活力和分化能力的情况下,可用铟 - 111标记人MSC,以便在临床试验中对输送至心脏的干细胞进行闪烁显像追踪。这为临床心血管试验中控制干细胞递送和剂量反应创造了一个重要工具。

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