Ebert Steven N, Taylor David G, Nguyen Ha-Long, Kodack David P, Beyers Ronald J, Xu Yaqin, Yang Zequan, French Brent A
Burnett College of Biomedical Sciences, University of Central Florida, 4000 Central Florida Boulevard, Orlando, Florida 32816, USA.
Stem Cells. 2007 Nov;25(11):2936-44. doi: 10.1634/stemcells.2007-0216. Epub 2007 Aug 9.
Despite rapid advances in the stem cell field, the ability to identify and track transplanted or migrating stem cells in vivo is limited. To overcome this limitation, we used magnetic resonance imaging (MRI) to detect and follow transplanted stem cells over a period of 28 days in mice using an established myocardial infarction model. Pluripotent mouse embryonic stem (mES) cells were expanded and induced to differentiate into beating cardiomyocytes in vitro. The cardiac-differentiated mES cells were then loaded with superparamagnetic fluorescent microspheres (1.63 microm in diameter) and transplanted into ischemic myocardium immediately following ligation and subsequent reperfusion of the left anterior descending coronary artery. To identify the transplanted stem cells in vivo, MRI was performed using a Varian Inova 4.7 Tesla scanner. Our results show that (a) the cardiac-differentiated mES were effectively loaded with superparamagnetic microspheres in vitro, (b) the microsphere-loaded mES cells continued to beat in culture prior to transplantation, (c) the transplanted mES cells were readily detected in the heart in vivo using noninvasive MRI techniques, (d) the transplanted stem cells were detected in ischemic myocardium for the entire 28-day duration of the study as confirmed by MRI and post-mortem histological analyses, and (e) concurrent functional MRI indicated typical loss of cardiac function, although significant amelioration of remodeling was noted after 28 days in hearts that received transplanted stem cells. These results demonstrate that it is feasible to simultaneously track transplanted stem cells and monitor cardiac function in vivo over an extended period using noninvasive MRI techniques.
尽管干细胞领域取得了快速进展，但在体内识别和追踪移植或迁移的干细胞的能力仍然有限。为了克服这一限制，我们使用磁共振成像（MRI）在建立的心肌梗死小鼠模型中，对移植的干细胞进行了为期28天的检测和追踪。多能小鼠胚胎干细胞（mES）在体外进行扩增并诱导分化为跳动的心肌细胞。然后将经心脏分化的mES细胞装载上超顺磁性荧光微球（直径1.63微米），并在左前降支冠状动脉结扎及随后再灌注后立即将其移植到缺血心肌中。为了在体内识别移植的干细胞，使用瓦里安Inova 4.7特斯拉扫描仪进行MRI检查。我们的结果表明：（a）经心脏分化的mES细胞在体外能有效地装载超顺磁性微球；（b）装载微球的mES细胞在移植前在培养物中继续跳动；（c）使用非侵入性MRI技术可在体内心脏中轻松检测到移植的mES细胞；（d）通过MRI和死后组织学分析证实，在研究的整个28天期间，均可在缺血心肌中检测到移植的干细胞；（e）同时进行的功能MRI显示心脏功能出现典型丧失，尽管在接受移植干细胞的心脏中，28天后观察到重塑有显著改善。这些结果表明，使用非侵入性MRI技术在体内长时间同时追踪移植的干细胞并监测心脏功能是可行的。
