In vivo magnetic resonance imaging of cell tropsim, trafficking mechanism, and therapeutic impact of human mesenchymal stem cells in a murine glioma model

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• 作者：Li-Ying Chien^a ; ¹ ; Jong-Kai Hsiao^b ; ^c ; ¹ ; Szu-Chun Hsu^d ; Ming Yao^e ; Chen-Wen Lu^b ; Hon-Man Liu^b ; Yao-Chang Chen^d ; Chung-Shi Yang^a ; Dong-Ming Huang^a ; ^{dmhuang@nhri.org.tw}
• 关键词：Nanoparticle ; MRI ; Brain ; Mesenchymal stem cell ; Transplantation
• 刊名：Biomaterials
• 出版年：2011
• 出版时间：April 2011
• 年：2011
• 卷：32
• 期：12
• 页码：3275-3284
• 全文大小：1316 K

文摘

Stem cells have offered much promise as delivery vehicles for brain tumor therapy, with the development of modalities to track the tumor tropism of stem cells receiving intense focus. Cellular magnetic resonance imaging (MRI) allows serial high-resolution in vivo detection of transplanted stem cells’ tropism toward gliomas in the mouse brain once these cells are internally labeled with iron oxide particles, but has been impeded by low labeling efficiencies. In this study, we describe the use of ferucarbotran and protamine (Fer-Pro) complexes for labeling human mesenchymal stem cells (hMSCs) for MRI tracking of glioma tropism in vivo. We found that Fer-Pro was not toxic and was highly efficient for labeling in vitro. Cell labeling with Fer-Pro promoted the migration of hMSCs toward glioma U87MG cells in vitro, which was mediated by stromal-derived factor-1/CXCR4 (SDF-1/CXCR4) signaling. Fer-Pro-labeled hMSCs could migrate specifically toward gliomas in vivo, which was observed with a clinical 1.5-T MRI system. The efficient labeling of Fer-Pro also allowed a tropic mechanism mediated by SDF-1/CXCR4 signaling to be detected by MRI in vivo. Additionally, the potential intrinsic inhibitory effect of hMSCs on glioma progression was estimated simultaneously. This is the first report to have used a clinical MRI modality to simultaneously study the migration, the therapeutic impact on tumors, and above all the trafficking mechanism of bone marrow-derived mesenchymal stem cells from human in a murine glioma xenograft model. The use of Fer-Pro for stem cell labeling may have potential clinical applications in stem cell guided therapy.