Superparamagnetic iron oxide-labeled Schwann cells and olfactory ensheathing cells can be traced in vivo by magnetic resonance imaging and retain functional properties after transplantation into the CNS
Superparamagnetic iron oxide-labeled Schwann cells and olfactory ensheathing cells can be traced in vivo by magnetic resonance imaging and retain functional properties after transplantation into the CNS
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DOI：
10.1523/jneurosci.3126-04.2004
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发表时间：
2004-11-03
影响因子：
5.3
通讯作者：
Franklin, RJM
中科院分区：
文献类型：
--
作者：
Dunning, MD;Lakatos, A;Franklin, RJM
雪旺细胞（SC）和嗅鞘细胞（OEC）移植已被实验证明，促进中枢神经系统轴突再生和髓鞘再生。为了将这项技术推进到临床环境中，重要的是能够通过非侵入性成像来跟踪移植细胞的命运。以前的研究，使用复杂的修饰过程，使造影剂的摄取，已经表明，在体外标记的细胞与顺磁性造影剂移植到啮齿动物的中枢神经系统可以使用磁共振成像（MRI）可视化。在这里，我们表明，SC和嗅鞘细胞有效地内化葡聚糖涂层超顺磁性氧化铁（SPIO）从培养基中的液相胞饮。移植到成年大鼠脊髓脱髓鞘的病灶区后，移植的SPIO标记的SC和OECs在麻醉大鼠中使用T-2加权MRI产生持续长达4周的信号降低。尽管在移植未标记的细胞后可辨别信号减少，但这与移植的标记细胞产生的信号减少是可区分的。SPIO标记的细胞受体中信号减少的区域与髓鞘再生的区域密切相关。由于标记细胞保留功能完整性至关重要，我们还表明SPIO标记的SC和OEC在移植到脱髓鞘局灶区域后能够正常髓鞘形成。这些研究证明了移植的干细胞和嗅鞘细胞的非侵入性成像的可行性，并代表了有前途的实验方法的临床应用的重要一步。
Schwann cell (SC) and olfactory ensheathing cell (OEC) transplantation has been shown experimentally to promote CNS axonal regeneration and remyelination. To advance this technique into a clinical setting it is important to be able to follow the fates of transplanted cells by noninvasive imaging. Previous studies, using complex modification processes to enable uptake of contrast agents, have shown that cells labeled in vitro with paramagnetic contrast agents transplanted into rodent CNS can be visualized using magnetic resonance imaging (MRI). Here we show that SCs and OECs efficiently internalize dextran-coated superparamagnetic iron oxide (SPIO) from the culture medium by fluid phase pinocytosis. After transplantation into focal areas of demyelination in adult rat spinal cord both transplanted SPIO-labeled SCs and OECs produce a signal reduction using T-2-weighted MRI in anesthetized rats that persists for up to 4 weeks. Although signal reduction was discernable after transplantation of unlabelled cells, this is nevertheless distinguishable from that produced by transplanted labeled cells. The region of signal reduction in SPIO-labeled cell recipients correlates closely with areas of remyelination. Because the retention of functional integrity by labeled cells is paramount, we also show that SPIO-labeled SCs and OECs are able to myelinate normally after transplantation into focal areas of demyelination. These studies demonstrate the feasibility of noninvasive imaging of transplanted SCs and OECs and represent a significant step toward the clinical application of promising experimental approaches.