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MRI 示踪聚乙二醇修饰的超顺磁性氧化铁标记胎盘间充质干细胞向荷胶质瘤干细胞小鼠模型中的归巢。

MRI tracking of polyethylene glycol-coated superparamagnetic iron oxide-labelled placenta-derived mesenchymal stem cells toward glioblastoma stem-like cells in a mouse model.

机构信息

a Department of Radiology , School of Medicine, College of Medicine, Taipei Medical University , Taipei , Taiwan.

b Department of Biological Science and Technology , China Medical University , Taichung , Taiwan.

出版信息

Artif Cells Nanomed Biotechnol. 2018;46(sup3):S448-S459. doi: 10.1080/21691401.2018.1499661. Epub 2018 Sep 8.

DOI:10.1080/21691401.2018.1499661
PMID:30198338
Abstract

Mesenchymal stem cells (MSCs) that display homing and infiltration properties towards tumor cells are a promising cellular targeting vector for brain tumor therapy but are limited to local-regional delivery in current preclinical models. Here, we investigated whether placenta-derived MSCs (P-MSCs) are a superior cellular vector for systemic targeting of glioblastoma stem-like cells (GSCs), with an imaging modality to real-time monitor the trafficking P-MSCs to glioblastoma sites. Results demonstrated that P-MSCs had greater migratory activity towards GSCs and across blood-brain barrier compared with bone marrow-derived MSCs, and this activity was enhanced by hypoxia precondition. Chemokine ligand 5 was identified as a chemoattractant responsible for the glioblastoma tropism of P-MSCs. Polyethylene glycol-coated superparamagnetic iron oxide (PEG-SPIO) was synthesized for cellular labelling and imaging P-MSCs, displaying high cellular uptake and no cytotoxic effect on P-MSCs cell proliferation or stemness property. The homing effects of intravenously administered PEG-SPIO-labelled P-MSCs towards intracerebral GSCs were able to be detected in mice models through T2-weighted magnetic resonance imaging (MRI). This study suggests the possibility of innovative systemic P-MSC-based cell therapy for aggressive GSCs, developing a state-of-the-art theranostic technique for real-time tracking of therapeutic P-MSCs tumor infiltration through cellular MRI.

摘要

间充质干细胞(MSCs)具有向肿瘤细胞归巢和浸润的特性,是脑肿瘤治疗有前途的细胞靶向载体,但在当前的临床前模型中仅限于局部区域递送。在这里,我们研究了胎盘来源的间充质干细胞(P-MSCs)是否是全身靶向神经胶质瘤干细胞(GSCs)的更好的细胞载体,并用一种成像方式实时监测 P-MSCs 向神经胶质瘤部位的迁移。结果表明,与骨髓来源的间充质干细胞相比,P-MSCs 对 GSCs 的迁移活性更高,并且可以穿过血脑屏障,这种活性通过缺氧预处理得到增强。趋化因子配体 5 被鉴定为负责 P-MSCs 神经胶质瘤趋向性的趋化因子。合成了聚乙二醇包覆的超顺磁性氧化铁(PEG-SPIO)用于细胞标记和成像 P-MSCs,显示出高细胞摄取率,对 P-MSCs 细胞增殖或干细胞特性没有细胞毒性作用。通过 T2 加权磁共振成像(MRI)在小鼠模型中可以检测到静脉内给予的 PEG-SPIO 标记的 P-MSCs 向脑内 GSCs 的归巢效应。这项研究表明了基于创新的全身 P-MSC 细胞治疗侵袭性 GSCs 的可能性,为通过细胞 MRI 实时跟踪治疗性 P-MSCs 肿瘤浸润开发了一种最先进的治疗诊断技术。

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