Centre of Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom .
Circ Cardiovasc Imaging. 2012 Jul;5(4):509-17. doi: 10.1161/CIRCIMAGING.112.972596. Epub 2012 Jul 10.
Cell therapy is an emerging and exciting novel treatment option for cardiovascular disease that relies on the delivery of functional cells to their target site. Monitoring and tracking cells to ensure tissue delivery and engraftment is a critical step in establishing clinical and therapeutic efficacy. The study aims were (1) to develop a Good Manufacturing Practice-compliant method of labeling competent peripheral blood mononuclear cells with superparamagnetic particles of iron oxide (SPIO), and (2) to evaluate its potential for magnetic resonance cell tracking in humans.
Peripheral blood mononuclear cells 1-5 × 10(9) were labeled with SPIO. SPIO-labeled cells had similar in vitro viability, migratory capacity, and pattern of cytokine release to unlabeled cells. After intramuscular administration, up to 10(8) SPIO-labeled cells were readily identifiable in vivo for at least 7 days using magnetic resonance imaging scanning. Using a phased-dosing study, we demonstrated that systemic delivery of up to 10(9) SPIO-labeled cells in humans is safe, and cells accumulating in the reticuloendothelial system were detectable on clinical magnetic resonance imaging. In a healthy volunteer model, a focus of cutaneous inflammation was induced in the thigh by intradermal injection of tuberculin. Intravenously delivered SPIO-labeled cells tracked to the inflamed skin and were detectable on magnetic resonance imaging. Prussian blue staining of skin biopsies confirmed iron-laden cells in the inflamed skin.
Human peripheral blood mononuclear cells can be labeled with SPIO without affecting their viability or function. SPIO labeling for magnetic resonance cell tracking is a safe and feasible technique that has major potential for a range of cardiovascular applications including monitoring of cell therapies and tracking of inflammatory cells. Clinical Trial Registration- URL: http://www.clinicaltrials.gov; Unique identifier: NCT00972946, NCT01169935.
细胞治疗是一种新兴的、令人兴奋的心血管疾病治疗新选择，依赖于将功能细胞递送至靶部位。监测和跟踪细胞以确保组织递送至并植入是建立临床和治疗疗效的关键步骤。本研究旨在：（1）开发一种符合良好生产规范的方法，用超顺磁性氧化铁（SPIO）标记有能力的外周血单个核细胞；（2）评估其在人体磁共振细胞跟踪中的应用潜能。
外周血单个核细胞 1-5×10(9) 用 SPIO 标记。SPIO 标记的细胞与未标记的细胞具有相似的体外活力、迁移能力和细胞因子释放模式。经肌内给药后，在至少 7 天内，使用磁共振成像扫描，体内可轻易识别多达 10(8) SPIO 标记的细胞。通过逐步剂量研究，我们证明在人体中系统递送至多达 10(9) SPIO 标记的细胞是安全的，并且可在临床磁共振成像上检测到蓄积在网状内皮系统中的细胞。在健康志愿者模型中，通过皮内注射结核菌素在大腿中诱导皮肤炎症病灶。静脉内递送至炎症皮肤的 SPIO 标记细胞可在磁共振成像上检测到。皮肤活检的普鲁士蓝染色证实了炎症皮肤中存在含铁细胞。
人外周血单个核细胞可用 SPIO 标记而不影响其活力或功能。用于磁共振细胞跟踪的 SPIO 标记是一种安全可行的技术，具有广泛的心血管应用潜能，包括细胞治疗监测和炎症细胞跟踪。临床试验注册- URL：http://www.clinicaltrials.gov；独特标识符：NCT00972946，NCT01169935。
