人胚干细胞源性畸胎瘤的序贯锰增强磁共振成像的治疗效果。
Theranostic effect of serial manganese-enhanced magnetic resonance imaging of human embryonic stem cell derived teratoma.
机构信息
Department of Medicine, Stanford University, Stanford, California, United States of America.
出版信息
Magn Reson Med. 2012 Aug;68(2):595-9. doi: 10.1002/mrm.23262. Epub 2011 Dec 21.
Although human embryonic stem cell (hESC) hold therapeutic potential, teratoma formation has deterred clinical translation. Manganese (Mn(2+)) enters metabolically active cells through voltage-gated calcium channels and subsequently, induces T(1) shortening. We hypothesized that serial manganese-enhanced MRI would have theranostic effect to assess hESC survival, teratoma formation, and hESC-derived teratoma reduction through intracellular accumulation of Mn(2+). Firefly luciferase transduced hESCs (hESC-Lucs) were transplanted into severe combined immunodeficient mouse hindlimbs to form teratoma. The chemotherapy group was injected with MnCl(2) intraperitoneally three times a week. The control group was given MnCl(2) only prior to manganese-enhanced MRI. Longitudinal evaluation by manganese-enhanced MRI and bioluminescence imaging 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 MnCl(2) enabled simultaneous monitoring and elimination of hESC-derived teratoma cells by higher intracellular accumulation of Mn(2+).
尽管人类胚胎干细胞（hESC）具有治疗潜力，但畸胎瘤的形成阻碍了其临床转化。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，通过 Mn(2+)的细胞内积累，连续锰增强 MRI 将具有治疗诊断作用，以评估 hESC 存活、畸胎瘤形成以及 hESC 衍生的畸胎瘤减少。转染萤火虫荧光素酶的 hESC（hESC-Lucs）被移植到严重联合免疫缺陷小鼠后肢中形成畸胎瘤。化疗组每周三次通过腹腔内注射 MnCl2。对照组仅在锰增强 MRI 之前给予 MnCl2。通过锰增强 MRI 和生物发光成像进行纵向评估。化疗组在第 6 周和第 8 周时显示出畸胎瘤体积和荧光素酶活性的显著减少。组织学显示化疗组的死亡细胞和 caspase 3 阳性细胞比例增加。MnCl2 的全身给药通过更高的细胞内 Mn(2+)积累，使 hESC 衍生的畸胎瘤细胞的同时监测和消除成为可能。
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