Division of Cardiology, Emory University School of Medicine, Atlanta, GA 30322, USA.
Small. 2013 Dec 9;9(23):4017-26. doi: 10.1002/smll.201300570. Epub 2013 Jun 13.
Cell therapies offer exciting new opportunities for effectively treating many human diseases. However, delivery of therapeutic cells by intravenous injection, while convenient, relies on the relatively inefficient process of homing of cells to sites of injury. To address this limitation, a novel strategy has been developed to load cells with superparamagnetic iron oxide nanoparticles (SPIOs), and to attract them to specific sites within the body by applying an external magnetic field. The feasibility of this approach is demonstrated using human mesenchymal stem cells (hMSCs), which may have a significant potential for regenerative cell therapies due to their ease of isolation from autologous tissues, and their ability to differentiate into various lineages and modulate their paracrine activity in response to the microenvironment. The efficient loading of hMSCs with polyethylene glycol-coated SPIOs is achieved, and it is found that SPIOs are localized primarily in secondary lysosomes of hMSCs and are not toxic to the cells. Further, the key stem cell characteristics, including the immunophenotype of hMSCs and their ability to differentiate, are not altered by SPIO loading. Through both experimentation and mathematical modeling, it is shown that, under applied magnetic field gradients, SPIO-containing cells can be localized both in vitro and in vivo. The results suggest that, by loading SPIOs into hMSCs and applying appropriate magnetic field gradients, it is possible to target hMSCs to particular vascular networks.
细胞治疗为有效治疗许多人类疾病提供了令人兴奋的新机会。然而，通过静脉注射输送治疗细胞虽然方便，但依赖于细胞归巢到损伤部位的相对低效过程。为了解决这个限制，已经开发了一种新策略，即将细胞加载到超顺磁氧化铁纳米颗粒（SPIOs）中，并通过施加外部磁场将其吸引到体内的特定部位。使用人骨髓间充质干细胞（hMSCs）证明了这种方法的可行性，由于其易于从自体组织中分离出来，以及能够分化为各种谱系并根据微环境调节其旁分泌活性，因此 hMSCs 具有显著的再生细胞治疗潜力。成功地将 hMSCs 用聚乙二醇包覆的 SPIOs 进行了负载，并且发现 SPIOs 主要定位于 hMSCs 的次级溶酶体中，并且对细胞没有毒性。此外，关键的干细胞特性，包括 hMSCs 的免疫表型及其分化能力，不会因 SPIO 负载而改变。通过实验和数学建模表明，在施加的磁场梯度下，含有 SPIO 的细胞可以在体外和体内进行定位。结果表明，通过将 SPIOs 加载到 hMSCs 中并施加适当的磁场梯度，可以将 hMSCs 靶向特定的血管网络。
