胚胎內(nèi)皮祖細胞(embryonic endothelial progenitor cells)的起源和命運,。
涉及移植到心肌梗塞發(fā)作后心臟受損區(qū)域的最佳干細胞療法常因細胞不能高效地歸巢到受損位點而遭受挫折,。然而,在大鼠模式動物中,,法國研究人員利用磁鐵來引導裝載用氧化鐵納米顆粒的細胞移動到關鍵部位,,從而促進血管內(nèi)注射的內(nèi)皮祖細胞(endothelial progenitor cell)更好地停留在心肌中。
法國國家健康與醫(yī)學研究院(INSERM)外科研究U633實驗室研究員Philippe Menasche博士說,,“細胞療法是一種大有希望的促進心肌再生和新血管形成的方法,,但是在當前,通過腔內(nèi)注入(intracavitary infusion)之后,,注入的細胞因不能發(fā)揮高效歸巢的作用而使得這種方法遭受難題,。我們的研究旨在通過讓用于移植的人臍帶血來源的內(nèi)皮祖細胞裝載氧化鐵納米顆粒,然后利用一種皮下植入的磁鐵讓細胞更好地位于和停留在心肌受損的試驗大鼠的心臟之中,,從而改善和控制細胞歸巢能力,。”
研究人員發(fā)現(xiàn)這些細胞產(chǎn)生的磁性足以能夠通過隨后植入的磁鐵來進行遠程操縱。
根據(jù)研究人員的說法,,客觀地評估這種促進血液中循環(huán)流通干細胞(circulating stem cells)歸巢的方法就是能夠在體內(nèi)追蹤它們的命運,。利用核磁共振成像(Magnatic Resonance Imaging, MRI)進行可視化觀察就可以實現(xiàn)這點。
Menasche博士說,,“我們發(fā)現(xiàn)利用MRI非侵入式地追蹤這些注入的細胞與免疫熒光或定量PCR實驗數(shù)據(jù)之間存在很好的關聯(lián),。”研究人員作出結(jié)論,,需要進一步開展研究以便在更為靠后的時間點上追蹤這些細胞。他們也注意到它們呈現(xiàn)出的歸巢能力可能因所使用的相對較小的細胞數(shù)量而受到削弱,。(生物谷:Bioon.com)
本文編譯自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.