Delo Dawn M, Olson John, Baptista Pedro M, D'Agostino Ralph B, Atala Anthony, Zhu Jian-Ming, Soker Shay
Wake Forest Institute for Regenerative Medicine, Wake Forest University Health Sciences, Winston-Salem, North Carolina 27157, USA.
Stem Cells Dev. 2008 Dec;17(6):1185-94. doi: 10.1089/scd.2008.0028.
Human stem cells from various sources have potential therapeutic applications. The clinical implementation of these therapies introduces the need for methods of noninvasive tracking of cells. The purpose of this study was to evaluate a high resolution magnetic resonance imaging (MRI) technique for in vivo detection and tracking of superparamagnetic micron sized iron oxide particle (MPIO)-labeled human amniotic fluid stem (hAFS) cells injected in the mouse heart. Because of the small subject size, MR signal and resolution of the in vivo MRI were increased using strong gradients, a 7.0 Tesla magnet, and an ECG and respiratory gated gradient echo sequence. MRI images of mouse heart were acquired during a 4 week course of this longitudinal study. At the end of the study, histological analysis was used to correlate cell localization with the MRI results. Introduction of MPIOs into hAFS had no significant effect upon cell proliferation and differentiation. Results of flow cytometry analysis indicated that hAFS cells remained labeled for up to 4 weeks. MRI of MPIO-labeled hAFS cells injected in agarose gels resulted in significant hypointense regions. Labeled hAFS cells injected into mouse hearts produced hypointense regions in the MR images that could be detected 24 hours and 7, 14, 21 and 28 days post injection. The co-localization of labeled cells within the hypointense regions was confirmed by histological analysis. These results indicate that high resolution MRI can be used successfully for noninvasive longitudinal tracking of hAFS cells injected in the mouse heart. The potential utility of this finding is that injected stem cells can be tracked in vivo and might serve to monitor cell survival, proliferation and integration into myocardial tissue.
来自各种来源的人类干细胞具有潜在的治疗应用价值。这些疗法的临床应用引发了对细胞非侵入性追踪方法的需求。本研究的目的是评估一种高分辨率磁共振成像(MRI)技术,用于在体内检测和追踪注射到小鼠心脏中的超顺磁性微米级氧化铁颗粒(MPIO)标记的人羊水干细胞(hAFS)。由于研究对象体积小,使用强梯度、7.0特斯拉磁体以及心电图和呼吸门控梯度回波序列来提高体内MRI的磁共振信号和分辨率。在这项纵向研究的4周过程中采集小鼠心脏的MRI图像。研究结束时,使用组织学分析将细胞定位与MRI结果相关联。将MPIO引入hAFS对细胞增殖和分化没有显著影响。流式细胞术分析结果表明,hAFS细胞在长达4周的时间内保持标记状态。对注射到琼脂糖凝胶中的MPIO标记的hAFS细胞进行MRI检查,结果显示出明显的低信号区域。注射到小鼠心脏中的标记hAFS细胞在注射后24小时以及7、14、21和28天的MR图像中产生低信号区域。通过组织学分析证实了标记细胞在低信号区域内的共定位。这些结果表明,高分辨率MRI可以成功用于对注射到小鼠心脏中的hAFS细胞进行非侵入性纵向追踪。这一发现的潜在用途是,可以在体内追踪注射的干细胞,这可能有助于监测细胞存活、增殖以及整合到心肌组织中的情况。