Oatp1a1增强MRI在小鼠卒中模型中活体追踪移植神经干细胞
本研究利用慢病毒载体使神经干细胞过表达Oatp1a1，证实其生物安全性及对Gd-EOB-DTPA的高效摄取，将预标记细胞移植至光血栓性脑缺血小鼠后，经3.0 T MRI在T1W图像上观察到高信号，持续至随访21天，组织学验证一致。基于Oatp1a1的正对比MRI策略可实现安全、特异的干细胞活体追踪。
要点
- Oatp1a1过表达NSCs可安全高效摄取Gd-EOB-DTPA，实现T1正对比标记。
- 移植后T1W高信号可持续21天，组织学证实与细胞位置一致。
- 该策略避免铁基MRI的内源性对比模糊，实现特异性追踪。
关键影像表现/征象
- Oatp1a1过表达NSCs在体外显著缩短纵向弛豫时间，促进Gd-EOB-DTPA摄取。
- 移植至脑梗死区后，标记NSCs在T1W图像上呈高信号，随访至21天仍可见。
- 组织学分析证实T1W高信号与移植细胞位置一致。
临床应用与阅片要点
- 阅片时关注T1W高信号是否位于梗死区及移植灶，结合随访判断细胞存活与迁移。
- 注意与梗死后内源性T1高信号（如出血、钙化）鉴别，必要时结合组织学或元素分析验证。
局限性
- 研究为小鼠模型，样本量未报告，结果向临床转化需进一步验证。
- 仅使用3.0 T MRI和Gd-EOB-DTPA，其他设备或对比剂适用性未知。
以上解读依据论文摘要（全文未开放获取或许可不允许翻译转载）。
英文原文（摘要）· 点击展开
RATIONALE AND OBJECTIVES: Neural stem cells (NSCs) represent a promising therapeutic avenue for ischemic stroke. A critical barrier to their clinical application is the challenge of monitoring their survival and location post-transplantation. While iron-based magnetic resonance imaging (MRI) is widely used for cell tracking, its utility is limited by ambiguous contrast due to endogenous sources like hemosiderin and potential compromises to cell safety from iron's biological activity. This study aimed to achieve precise, specific, and longitudinal tracking of NSCs in ischemic stroke using a novel positive reporter gene system.
MATERIALS AND METHODS: We first generated organic anion transporting polypeptide 1a1 (Oatp1a1)-overexpressing NSCs using lentiviral vectors and confirmed their biosafety and efficient uptake of gadolinium-ethoxybenzyl-diethylenetriaminepentaacetic acid (Gd-EOB-DTPA). Subsequently, these pre-labeled cells were transplanted into mice with photothrombotic ischemia under MRI guidance. Finally, in vivo tracking was performed via 3.0 T MRI, supported by ex vivo histological and elemental analyses.
RESULTS: Stable Oatp1a1 expression in transduced NSCs and biosafety of Oatp1a1 overexpression were confirmed. In vitro, overexpression of Oatp1a1 promoted Gd-EOB-DTPA uptake, significantly reducing the longitudinal relaxation time. Following the injection of Gd-EOB-DTPA-labeled NSCs into the area of cerebral infarction, these NSCs appeared as hyperintense signals on T1W images for up to 21 days of follow-up, as confirmed by histology.
CONCLUSIONS: The Oatp1a1-based positive-contrast MRI strategy enables safe and specific in vivo tracking of stem cells, facilitating the clinical translation of therapies for ischemic stroke.
引用
- Wen Q, Zhu W, Zhang Q, et al. In vivo Tracking of Transplanted Neural Stem Cells Using Oatp1a1-Enhanced Magnetic Resonance Imaging in a Mouse Model of Stroke. Acad Radiol. 2026. PMID: 42203628. doi:10.1016/j.acra.2026.04.050
供执业医师工作参考，不替代临床判断；数值与分级以指南原文为准。