Gene therapy of experimental brain tumors using neural progenitor cells
Gene therapy of experimental brain tumors using neural progenitor cells
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DOI：
10.1038/74710
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发表时间：
2000-04-01
期刊：
影响因子：
82.9
通讯作者：
Finocchiaro, G
中科院分区：
文献类型：
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作者：
Benedetti, S;Pirola, B;Finocchiaro, G
胶质母细胞瘤是原发性脑肿瘤中最常见和最恶性的肿瘤，具有非常差的增殖性。胶质母细胞瘤的基因治疗受到病毒载体存活时间短和难以到达浸润脑实质的胶质母细胞瘤细胞的限制。神经干细胞/祖细胞可以经过工程改造以产生治疗分子，并有潜力克服这些限制，因为它们可以像肿瘤细胞一样沿着白色移动，并稳定地移植到大脑中（2，3）。逆转录病毒介导的白细胞介素-4基因转移是治疗大鼠脑胶质母细胞瘤的有效方法（4）。在这里，我们将白细胞介素-4基因转移到C57 BL 6 J小鼠原代神经祖细胞中，并将这些细胞注射到已建立的同基因脑胶质母细胞瘤中。这导致了大多数荷瘤小鼠的存活。我们通过将来自Sprague-Dawley大鼠的永生化神经前体细胞植入C6胶质母细胞瘤中获得了类似的结果。我们还通过磁共振成像记录了大肿瘤的逐渐消失，并在注射后几周检测到5-溴脱氧尿苷标记的祖细胞。这些发现支持了一种新的脑肿瘤基因治疗方法，该方法基于移植神经干细胞产生治疗分子。
Glioblastomas, the most frequent and malignant of primary brain tumors, have a very poor prognosis'. Gene therapy of glioblastomas is limited by the short survival of viral vectors and by their difficulty in reaching glioblastoma cells infiltrating the brain parenchyma. Neural stem/progenitor cells can be engineered to produce therapeutic molecules and have the potential to overcome these limitations because they may travel along the white matter, like neoplastic cells, and engraft stably into the brain(2,3). Retrovirus-mediated transfer of the gene for interleukin-4 is an effective treatment for rat brain glioblastomas(4). Here, we transferred the gene for interleukin-4 into C57BL6J mouse primary neural progenitor cells and injected those cells into established syngeneic brain glioblastomas. This led to the survival of most tumor-bearing mice. We obtained similar results by implanting immortalized neural progenitor cells derived from Sprague-Dawley rats into C6 glioblastomas. We also documented by magnetic resonance imaging the progressive disappearance of large tumors, and detected 5-bromodeoxyuridine-labeled progenitor cells several weeks after the injection. These findings support a new approach for gene therapy of brain tumors, based on the grafting of neural stem cells producing therapeutic molecules.