细胞磁共振成像不能区分磁标细胞的存活状态

Cellular MR imaging couldn’t reflect the survivorship or death of cells labeled with superparamagnetic iron oxides

目的探讨不同状态下磁标记间充质干细胞(MSCs)的体内外磁共振(MR)成像特点,明确MR对细胞存活状态是否有鉴别诊断价值。方法分离培养猪骨髓MSCs,用超顺磁性铁纳米颗粒(SPIO)标记细胞24h。对未标记MSCs、存活的SPIO-MSCs、死亡的SPIO-MSCs、单纯SPIO进行体外凝胶内1.5TMR成像;开胸结扎前降支建立猪心肌梗死模型,于梗死交界区心肌内直接注射未标记MSCs、存活的SPIO-MSCs、死亡的SPIO-MSCs和单纯SPIO,然后进行体内T2*WI-flash序列MR成像。结果存活的SPIO-MSCs、死亡的SPIO-MSCs和单纯SPIO在体内外T2*WI-flash序列MR图像上均显示为低信号区,单凭图像无法区分。结论细胞MR成像无法区分组织磁标细胞、游离铁和含铁病变,因此对长期细胞示踪结果的解读应该慎重。

Objective To explore whther there exists any difference in cellular MR imaging between alive cells labeled with superparamagnetic iron oxides （SPIO）, dead cells labeled with （SPIO）, unlabeled cells and free SPIO, then to deduce the value of MR imaging in long-term cell tracking. Methods Swine bone marrow mesenchymal stem cells （MSCs） were isolated and culture-expanded 3 passages in vitro, then magnetically labeled by incubation with SHU 555A （25 μg Fe/mL, Resovist, Schering） in culture medium for 24 hours with 750 ng/mL poly-L-lysine （PLL; average MW 275 kDa） added 1 hour before incubation. The alive 5×105 SPIO-MSCs, dead 5×105 SPIO-MSCs, unlabeled 5×105 MSCs and free SPIO underwent MR imaging with T1-and T2-weighted spin-echo and fast field-echo sequences at a clinical 1.5 T MR system, respectively. Then, alive 1×106 SPIO-MSCs, dead 1×106 SPIO-MSCs, unlabeled 1×106 MSCs and free SPIO were transextracardially implanted into the peri-infracted myocardium approximately 2 week following the ligation of left anterior descending coronary artery in 4 swines respectively, then performed 1.5-T MR imaging at 3 days after injection. Results Compared with the unlabeled MSCs, the iron-containing groups, cncluding the alive SPIO-MSCs, dead SPIO-MSCs and free SPIO, featured low signal intensity areas with the T2＊WI flash scanning sequence. However, they couldn’t differentiate from each other on MR images in vitro and in vivo. Conclusion Cellular MR imaging couldn’t reflect the survivorship or death of cells labeled with SPIO, suggesting the interpretation for long-term cell tracking should be prudent.