胚胎内皮祖细胞(embryonic endothelial progenitor cells)的起源和命运。
涉及移植到心肌梗塞发作后心脏受损区域的最佳干细胞疗法常因细胞不能高效地归巢到受损位点而遭受挫折。然而,在大鼠模式动物中,法国研究人员利用磁铁来引导装载用氧化铁纳米颗粒的细胞移动到关键部位,从而促进血管内注射的内皮祖细胞(endothelial progenitor cell)更好地停留在心肌中。
法国国家健康与医学研究院(INSERM)外科研究U633实验室研究员Philippe Menasche博士说,“细胞疗法是一种大有希望的促进心肌再生和新血管形成的方法,但是在当前,通过腔内注入(intracavitary infusion)之后,注入的细胞因不能发挥高效归巢的作用而使得这种方法遭受难题。我们的研究旨在通过让用于移植的人脐带血来源的内皮祖细胞装载氧化铁纳米颗粒,然后利用一种皮下植入的磁铁让细胞更好地位于和停留在心肌受损的试验大鼠的心脏之中,从而改善和控制细胞归巢能力。”
研究人员发现这些细胞产生的磁性足以能够通过随后植入的磁铁来进行远程操纵。
根据研究人员的说法,客观地评估这种促进血液中循环流通干细胞(circulating stem cells)归巢的方法就是能够在体内追踪它们的命运。利用核磁共振成像(Magnatic Resonance Imaging, MRI)进行可视化观察就可以实现这点。
Menasche博士说,“我们发现利用MRI非侵入式地追踪这些注入的细胞与免疫荧光或定量PCR实验数据之间存在很好的关联。”研究人员作出结论,需要进一步开展研究以便在更为靠后的时间点上追踪这些细胞。他们也注意到它们呈现出的归巢能力可能因所使用的相对较小的细胞数量而受到削弱。(生物谷:Bioon.com)
本文编译自Magnet helps target transplanted iron-loaded cells to key areas of heart
doi:
PMC:
PMID:22080748
Can Magnetic Targeting of Magnetically Labeled Circulating Cells Optimize Intramyocardial Cell Retention?
Chaudeurge A, Wilhelm C, Chen-Tournoux A, Farahmand P, Bellamy V, Autret G, Ménager C, Hagège A, Larghéro J, Gazeau F, Clément O, Menasché P
Aims: Therapeutic intracavitary stem cell infusion currently suffers from poor myocardial homing. We examined whether cardiac cell retention could be enhanced by magnetic targeting of endothelial progenitor cells (EPCs) loaded with iron oxide nanoparticles.Methods and Results: EPCs were magnetically labeled with citrate-coated iron oxide nanoparticles. Cell proliferation, migration and CXCR4 chemokine receptor expression were assessed in different labeling conditions and no adverse effects of the magnetic label were observed. The magnetophoretic mobility of labeled EPCs was determined in vitro, with the same magnet as that subsequently used in vivo. Coronary artery occlusion was induced for 30 minutes in 36 rats (31 survivors), followed by 20 minutes of reperfusion. The rats were randomized to receive, during brief aortic cross-clamping, direct intraventricular injection of culture medium (n=7) or magnetically labeled EPCs (n=24), with (n=14) or without (n=10) subcutaneous insertion of a magnet over the chest cavity (n=14). The hearts were explanted 24 h later and engrafted cells were visualized by magnetic resonance imaging (MRI) of the heart at 1.5 T. Their abundance in the myocardium was also analyzed semi-quantitatively by immunofluorescence, and quantitatively by real time polymerase chain reaction (RT-PCR). Although differences in cell retention between groups failed to be statistically significant using RT-PCR quantification, due to the variability of the animal model, immunostaining showed that the average number of engrafted EPCs was significantly ten times higher with than without magnetic targeting. There was thus a consistent trend favoring the magnet-treated hearts, thereby suggesting magnetic targeting as a potentially new mean of enhancing myocardial homing of intravascularly delivered stem cells.Conclusion: Magnetic targeting has the potential to enhance myocardial retention of intravascularly delivered endothelial progenitor cells.