Genetically Engineered Multilineage-Differentiating Stress-Enduring Cells as Cellular Vehicles against Malignant Gliomas.
Genetically Engineered Multilineage-Differentiating Stress-Enduring Cells as Cellular Vehicles against Malignant Gliomas.
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DOI：
10.1016/j.omto.2017.06.001
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发表时间：
2017-09-15
期刊：
影响因子：
--
通讯作者：
Namba H
中科院分区：
文献类型：
--
作者：
Yamasaki T;Wakao S;Kawaji H;Koizumi S;Sameshima T;Dezawa M;Namba H
恶性胶质瘤是成人最常见的恶性脑肿瘤，因其侵袭性强，治疗困难。基于单纯疱疹病毒胸苷激酶(HSVtk)/更昔洛韦（GCV）系统的酶/前药自杀基因治疗是治疗恶性胶质瘤的有效策略。在目前的研究中，我们评估了多谱系分化应力持久（Muse）细胞的治疗，Muse细胞是内源性的非致瘤性多能干细胞，作为HSVtk基因的载体，很容易从骨髓中收集到SSEA-3+细胞。人Muse细胞在体内和体外均表现出对胶质瘤细胞的迁移活性。HSVtk基因转导的Muse细胞（Muse-tk细胞）细胞数量仅为U87人胶质瘤细胞的1/32，完全根除了裸鼠大脑中的U87胶质瘤，显示出强大的体内旁观者效应。裸鼠脑内预先存在的颅内U87胶质瘤瘤内注射Muse-tk细胞，然后腹腔注射GCV，在2周内显著缩小，10只治疗小鼠中有4只存活超过200天。这些发现表明瘤内注射Muse-tk细胞后全身给药是安全有效的，异体Muse-tk细胞药物自杀基因治疗恶性胶质瘤在临床上是可行的。
Malignant glioma, the most common malignant brain tumor in adults, is difficult to treat due to its aggressive invasive nature. Enzyme/prodrug suicide gene therapy based on the herpes simplex virus thymidine kinase (HSVtk)/ganciclovir (GCV) system is an efficient strategy for treating malignant gliomas. In the present study, we evaluated treatment with multilineage-differentiating stress-enduring (Muse) cells, which are endogenous non-tumorigenic pluripotent-like stem cells that are easily collectable from the bone marrow as SSEA-3+ cells, as carriers of the HSVtk gene. Human Muse cells showed potent migratory activity toward glioma cells both in vitro and in vivo. HSVtk gene-transduced Muse cells (Muse-tk cells) at a cell number of only 1/32 that of U87 human glioma cells completely eradicated U87 gliomas in nude mouse brains, showing a robust in vivo bystander effect. Pre-existing intracranial U87 gliomas in nude mouse brains injected intratumorally with Muse-tk cells followed by intraperitoneal GCV administration were significantly reduced in size within 2 weeks, and 4 of 10 treated mice survived over 200 days. These findings suggest that intratumoral Muse-tk cell injection followed by systemic GCV administration is safe and effective and that allogeneic Muse-tk cell-medicated suicide gene therapy for malignant glioma is clinically feasible.
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影响因子：
11.5
作者：
Hung, SC;Deng, WP;Gelovani, JG
通讯作者：
Gelovani, JG
影响因子：
3.5
作者：
Li, SY;Tokuyama, T;Namba, H
通讯作者：
Namba, H
DOI：
10.1073/pnas.0911647107
发表时间：
2010-05-11
影响因子：
11.1
作者：
Kuroda, Yasumasa;Kitada, Masaaki;Dezawa, Mari
通讯作者：
Dezawa, Mari
影响因子：
4.1
作者：
Sanai, Nader;Polley, Mei-Yin;Berger, Mitchel S.
通讯作者：
Berger, Mitchel S.
DOI：
10.1073/pnas.97.23.12846
发表时间：
2000-11-07
影响因子：
11.1
作者：
Aboody, KS;Brown, A;Snyder, EY
通讯作者：
Snyder, EY