Evaluation of Intracellular Labeling With Micron-Sized Particles of Iron Oxide (MPIOs) as a General Tool for In Vitro and In Vivo Tracking of Human Stem and Progenitor Cells

Evaluation of Intracellular Labeling With Micron-Sized Particles of Iron Oxide (MPIOs) as a General Tool for In Vitro and In Vivo Tracking of Human Stem and Progenitor Cells
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DOI:
10.3727/096368911x627598
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发表时间:
2012-01-01
影响因子:
3.3
通讯作者:
Glover, Joel C.
Glover, Joel C.
中科院分区:
医学4区
文献类型:
--
作者:
Boulland, Jean-Luc;Leung, Doreen S. Y.;Glover, Joel C.

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基于磁共振成像(MRI)的跟踪作为更好地了解体内干细胞动力学的一种手段越来越受到关注。由于相对于较小的氧化铁颗粒具有上级可检测性,用微米尺寸的氧化铁颗粒(MPIO)进行细胞内标记提供了一种实用的基于MRI的方法。然而,关于跨细胞类型的一般效用和MPIO标记人干细胞对细胞活力的影响的信息不足。我们标记了六种不同来源的人类细胞类型:骨髓间充质干细胞(MSC),脂肪组织间充质干细胞(ASC),推定成人神经干细胞(ad-NSC),胎儿神经祖细胞(f-NPCs),神经胶质瘤细胞系(U87),胶质母细胞瘤肿瘤干细胞(GSC),两种不同大小的MPIO(0.9和2.84 μ m)。不同细胞类型的标记和吸收效率差异很大。在体外测试了一般细胞功能的几个参数。标记和未标记的细胞之间的增殖率,有丝分裂持续时间,随机运动,并分化为特定的表型的能力只有很小的差异。在鸡胚和严重联合免疫缺陷(SCID)小鼠体内的行为进行了测试。死后组织学检查显示标记细胞存活并能整合到各种组织中。在SCID小鼠中进行的几周基于MRI的跟踪显示,注射到大脑中的标记GSC和f-NPC表现出与未标记细胞相似的易位,并且与先前研究中描述的迁移行为所预期的一样。结果支持基于MPIO的细胞跟踪作为一个普遍有用的工具,在体内的人类干细胞动力学的研究。
Magnetic resonance imaging (MRI)-based tracking is increasingly attracting attention as a means of better understanding stem cell dynamics in vivo. Intracellular labeling with micrometer-sized particles of iron oxide (MPIOs) provides a practical MRI-based approach due to superior detectability relative to smaller iron oxide particles. However, insufficient information is available about the general utility across cell types and the effects on cell vitality of MPIO labeling of human stem cells. We labeled six human cell types from different sources: mesenchymal stem cells derived from bone marrow (MSCs), mesenchymal stem cells derived from adipose tissue (ASCs), presumptive adult neural stem cells (ad-NSCs), fetal neural progenitor cells (f-NPCs), a glioma cell line (U87), and glioblastoma tumor stem cells (GSCs), with two different sizes of MPIOs (0.9 and 2.84 mu m). Labeling and uptake efficiencies were highly variable among cell types. Several parameters of general cell function were tested in vitro. Only minor differences were found between labeled and unlabeled cells with respect to proliferation rate, mitotic duration, random motility, and capacity for differentiation to specific phenotypes. In vivo behavior was tested in chicken embryos and severe combined immunodeficient (SCID) mice. Postmortem histology showed that labeled cells survived and could integrate into various tissues. MRI-based tracking over several weeks in the SCID mice showed that labeled GSCs and f-NPCs injected into the brain exhibited translocations similar to those seen for unlabeled cells and as expected from migratory behavior described in previous studies. The results support MPIO-based cell tracking as a generally useful tool for studies of human stem cell dynamics in vivo.