Theranostic effect of serial manganese-enhanced magnetic resonance imaging of human embryonic stem cell derived teratoma.
Theranostic effect of serial manganese-enhanced magnetic resonance imaging of human embryonic stem cell derived teratoma.
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DOI：
10.1002/mrm.23262
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发表时间：
2012-08
影响因子：
3.3
通讯作者：
Yang, Phillip C.
中科院分区：
文献类型：
--
作者：
Chung, Jaehoon;Dash, Rajesh;Kee, Kehkooi;Barral, Joelle K.;Kosuge, Hisanori;Robbins, Robert C.;Nishimura, Dwight;Reijo-Pera, Renee A.;Yang, Phillip C.
虽然hESC具有治疗潜力，但畸胎瘤的形成阻碍了临床转化。锰（Mn 2+）通过电压门控钙通道进入代谢活跃的细胞，随后诱导T1缩短。我们假设连续MEMRI将具有治疗诊断作用，以评估hESC存活、畸胎瘤形成和通过细胞内Mn 2+积累减少hESC衍生畸胎瘤。将萤火虫荧光素酶转导的hESC（hESC-Lucs）移植到SCID小鼠后肢中以形成畸胎瘤。化疗组每周3次腹腔注射MnCl 2。对照组仅在MEMRI前给予MnCl 2。通过MEMRI和生物发光成像（BLI）进行纵向评价。化疗组在第6周和第8周显示畸胎瘤体积和荧光素酶活性显著降低。组织学检查显示化疗组死亡细胞和caspase 3阳性细胞比例增加。MnCl 2的全身给药能够通过较高的Mn 2+细胞内积累同时监测和消除hESC衍生的畸胎瘤细胞。
Although hESCs hold therapeutic potential, teratoma formation has deterred clinical translation. Manganese (Mn2+) enters metabolically active cells through voltage-gated calcium channels and, subsequently, induces T1 shortening. We hypothesized that serial MEMRI would have theranostic effect to assess hESC survival, teratoma formation, and hESC-derived teratoma reduction through intracellular accumulation of Mn2+. Firefly luciferase transduced hESCs (hESC-Lucs) were transplanted into SCID mouse hindlimbs to form teratoma. The chemotherapy group was injected with MnCl2 IP three times a week. The control group was given MnCl2 only prior to MEMRI. Longitudinal evaluation by MEMRI and bioluminescence imaging (BLI) was performed. The chemotherapy group showed significant reduction in the teratoma volume and luciferase activity at weeks 6 and 8. Histology revealed increased proportion of dead cells and caspase 3 positive cells in the chemotherapy group. Systemic administration of MnCl2 enabled simultaneous monitoring and elimination of hESC-derived teratoma cells by higher intracellular accumulation of Mn2+.
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