Functional investigations on human mesenchymal stem cells exposed to magnetic fields and labeled with clinically approved iron nanoparticles.
Functional investigations on human mesenchymal stem cells exposed to magnetic fields and labeled with clinically approved iron nanoparticles.
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DOI：
10.1186/1471-2121-11-22
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发表时间：
2010-04-06
期刊：
影响因子：
--
通讯作者：
Schlemmer HP
中科院分区：
文献类型：
--
作者：
Schäfer R;Bantleon R;Kehlbach R;Siegel G;Wiskirchen J;Wolburg H;Kluba T;Eibofner F;Northoff H;Claussen CD;Schlemmer HP
对于间充质干细胞（MSCs）的临床应用，标记和跟踪是至关重要的，以评估细胞的分布和归巢。磁共振成像（MRI）已成功建立检测标记的超顺磁性氧化铁颗粒（SPIO）的MSC。尽管最初的报道表明用SPIO标记MSC是安全的而不影响MSC的生物学，但最近的研究报道了SPIO标记对MSC的代谢和功能的影响。将细胞和组织暴露于高磁场是MRI的功能原理。在这项研究中，我们建立了创新的标记协议，为人类骨髓间充质干细胞使用临床上建立SPIO结合磁场和功能的影响（迁移试验，定量的集落形成单位，基因和蛋白质表达的分析和分析的增殖能力，活力和分化潜力）的磁场未标记和标记的人类骨髓间充质干细胞。为了评价成像特性，进行了每个细胞的总铁负荷（TIL）的定量、电子显微镜检查和3.0 T下的MRI。用SPIO标记的人MSC永久暴露于磁场中，根据磁通线排列和生长。与未暴露于磁场的SPIO标记的MSC相比，在用SPIO标记后将MSC暴露于磁场显著增强了TIL，导致优化的成像特性（检测限：1，000个MSC）。在TIL和成像特性方面，标记后立即暴露于磁场优于24 h后暴露上级。在功能水平上，qRT-PCR检测到磁场作用抑制了标记MSCs的集落形成能力，并导致标记MSCs在成脂分化过程中脂蛋白脂酶和过氧化物酶体增殖物激活受体-γ的表达增强，而未标记MSCs在成骨分化过程中碱性磷酸酶的表达降低。此外，微阵列分析显示，暴露标记的MSC磁场导致上调的CD 93 mRNA和钙粘蛋白7 mRNA和下调的锌指FYVE结构域mRNA。未标记的MSC暴露于磁场导致CD 93 mRNA，脂质运载蛋白6 mRNA，唾液酸乙酰酯酶mRNA和嗅觉受体mRNA的上调和泛素1 mRNA的下调。磁场暴露对标记或未标记MSCs的迁移能力、存活能力、增殖率和软骨分化能力均无影响。在我们的研究中，建立了一种创新的标记方案，用于通过MRI使用SPIO结合磁场来跟踪MSC。SPIO和静磁场均被确定为影响人MSC功能生物学的独立因素。需要进一步的体内研究来阐明磁场与干细胞生物学相互作用的分子机制。
For clinical applications of mesenchymal stem cells (MSCs), labeling and tracking is crucial to evaluate cell distribution and homing. Magnetic resonance imaging (MRI) has been successfully established detecting MSCs labeled with superparamagnetic particles of iron oxide (SPIO). Despite initial reports that labeling of MSCs with SPIO is safe without affecting the MSC's biology, recent studies report on influences of SPIO-labeling on metabolism and function of MSCs. Exposition of cells and tissues to high magnetic fields is the functional principle of MRI. In this study we established innovative labeling protocols for human MSCs using clinically established SPIO in combination with magnetic fields and investigated on functional effects (migration assays, quantification of colony forming units, analyses of gene and protein expression and analyses on the proliferation capacity, the viability and the differentiation potential) of magnetic fields on unlabeled and labeled human MSCs. To evaluate the imaging properties, quantification of the total iron load per cell (TIL), electron microscopy, and MRI at 3.0 T were performed. Human MSCs labeled with SPIO permanently exposed to magnetic fields arranged and grew according to the magnetic flux lines. Exposure of MSCs to magnetic fields after labeling with SPIO significantly enhanced the TIL compared to SPIO labeled MSCs without exposure to magnetic fields resulting in optimized imaging properties (detection limit: 1,000 MSCs). Concerning the TIL and the imaging properties, immediate exposition to magnetic fields after labeling was superior to exposition after 24 h. On functional level, exposition to magnetic fields inhibited the ability of colony formation of labeled MSCs and led to an enhanced expression of lipoprotein lipase and peroxisome proliferator-activated receptor-γ in labeled MSCs under adipogenic differentiation, and to a reduced expression of alkaline phosphatase in unlabeled MSCs under osteogenic differentiation as detected by qRT-PCR. Moreover, microarray analyses revealed that exposition of labeled MSCs to magnetic fields led to an up regulation of CD93 mRNA and cadherin 7 mRNA and to a down regulation of Zinc finger FYVE domain mRNA. Exposition of unlabeled MSCs to magnetic fields led to an up regulation of CD93 mRNA, lipocalin 6 mRNA, sialic acid acetylesterase mRNA, and olfactory receptor mRNA and to a down regulation of ubiquilin 1 mRNA. No influence of the exposition to magnetic fields could be observed on the migration capacity, the viability, the proliferation rate and the chondrogenic differentiation capacity of labeled or unlabeled MSCs. In our study an innovative labeling protocol for tracking MSCs by MRI using SPIO in combination with magnetic fields was established. Both, SPIO and the static magnetic field were identified as independent factors which affect the functional biology of human MSCs. Further in vivo investigations are needed to elucidate the molecular mechanisms of the interaction of magnetic fields with stem cell biology.
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影响因子：
3.3
作者：
Kim, Daehong;Chun, Byoung-Gi;Song, Jihwan
通讯作者：
Song, Jihwan
影响因子：
4.4
作者：
Bohlson, SS;Silva, R;Tenner, AJ
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Tenner, AJ
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2.9
作者：
Pawelczyk, Edyta;Arbab, Ali S.;Frank, Joseph A.
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Frank, Joseph A.
影响因子：
5.2
作者：
Kern, Susanne;Eichler, Hermann;Bieback, Karen
通讯作者：
Bieback, Karen
影响因子：
37.8
作者：
Flacke, S;Fischer, S;Lanza, GM
通讯作者：
Lanza, GM