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