Loebinger Michael R, Kyrtatos Panagiotis G, Turmaine Mark, Price Anthony N, Pankhurst Quentin, Lythgoe Mark F, Janes Sam M
Centre for Respiratory Research, Rayne Institute, University College London, London, United Kingdom.
Cancer Res. 2009 Dec 1;69(23):8862-7. doi: 10.1158/0008-5472.CAN-09-1912. Epub 2009 Nov 17.
The ability of mesenchymal stem cells (MSC) to specifically home to tumors has suggested their potential use as a delivery vehicle for cancer therapeutics. MSC integration into tumors has been shown in animal models using histopathologic techniques after animal sacrifice. Tracking the delivery and engraftment of MSCs into human tumors will need in vivo imaging techniques. We hypothesized that labeling MSCs with iron oxide nanoparticles would enable in vivo tracking with magnetic resonance imaging (MRI). Human MSCs were labeled in vitro with superparamagnetic iron oxide nanoparticles, with no effect on differentiation potential, proliferation, survival, or migration of the cells. In initial experiments, we showed that as few as 1,000 MSCs carrying iron oxide nanoparticles can be detected by MRI one month after their coinjection with breast cancer cells that formed subcutaneous tumors. Subsequently, we show that i.v.- injected iron-labeled MSCs could be tracked in vivo to multiple lung metastases using MRI, observations that were confirmed histologically. This is the first study to use MRI to track MSCs to lung metastases in vivo. This technique has the potential to show MSC integration into human tumors, allowing early-phase clinical studies examining MSC homing in patients with metastatic tumors.
间充质干细胞（MSC）特异性归巢至肿瘤的能力表明其有潜力用作癌症治疗药物的递送载体。在动物模型中，通过动物处死后的组织病理学技术已证实MSC可整合到肿瘤中。追踪MSC在人类肿瘤中的递送和植入需要体内成像技术。我们假设用氧化铁纳米颗粒标记MSC能够通过磁共振成像（MRI）进行体内追踪。人MSC在体外被超顺磁性氧化铁纳米颗粒标记，对细胞的分化潜能、增殖、存活或迁移没有影响。在初步实验中，我们表明，与形成皮下肿瘤的乳腺癌细胞共注射一个月后，MRI能够检测到少至1000个携带氧化铁纳米颗粒的MSC。随后，我们表明，静脉注射铁标记的MSC能够通过MRI在体内追踪到多个肺转移灶，组织学观察证实了这一结果。这是第一项使用MRI在体内追踪MSC至肺转移灶的研究。该技术有潜力显示MSC整合到人类肿瘤中，从而开展早期临床研究，检测转移性肿瘤患者体内的MSC归巢情况。
