Adipose-derived Stem Cells as Therapeutic Delivery Vehicles of an Oncolytic Virus for Glioblastoma
Adipose-derived Stem Cells as Therapeutic Delivery Vehicles of an Oncolytic Virus for Glioblastoma
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DOI：
10.1038/mt.2009.265
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发表时间：
2010-02-01
影响因子：
12.4
通讯作者：
Caldas, Hannah
中科院分区：
文献类型：
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作者：
Josiah, Darnell T.;Zhu, Dongqin;Caldas, Hannah
多形性胶质母细胞瘤（GBM）占原发性恶性脑肿瘤的大部分，尽管进行了广泛的手术切除、放疗和化疗，但实际上仍然无法治愈。治疗困难是由于其特殊的浸润性质和融入正常脑组织的倾向。长期幸存者很少见，患者的中位生存期约为 1 年。使用成体干细胞作为抗癌药物的细胞递送载体是一种新颖且有吸引力的治疗策略。我们假设脂肪源性干细胞（ADSC）具有将粘液瘤病毒归巢并递送至神经胶质瘤细胞和实验性神经胶质瘤的能力。我们用 vMyxgfp 感染 ADSC，发现它们允许粘液瘤病毒复制。 ADSC 支持单轮和多轮复制，从而实现高效感染。此外，我们观察到对 ADSC 活力没有显着影响。我们在三维测定中将荧光标记的 GBM 细胞与粘液瘤病毒感染的 ADSC 共培养，并观察到成功的交叉感染和几乎完全在 GBM 细胞中伴随的细胞死亡。在远离肿瘤的颅内注射 vMyxgfp-ADSC 的体内原位研究表明，粘液瘤病毒是由 ADSC 传递的，从而导致存活率显着增加。我们的数据表明，ADSC 有望成为脑肿瘤溶瘤病毒（特别是粘液瘤病毒）的新载体。
Glioblastoma multiforme (GBM) accounts for the majority of primary malignant brain tumors and remains virtually incurable despite extensive surgical resection, radiotherapy, and chemotherapy. Treatment difficulty is due to its exceptional infiltrative nature and proclivity to integrate into normal brain tissue. Long-term survivors are rare, and median survival for patients is about 1 year. Use of adult stem cells as cellular delivery vehicles for anticancer agents is a novel attractive therapeutic strategy. We hypothesized that adipose-derived stem cells (ADSCs) possess the ability to home and deliver myxoma virus to glioma cells and experimental gliomas. We infected ADSCs with vMyxgfp and found them to be permissive for myxoma virus replication. ADSCs supported single and multiple rounds of replication leading to productive infection. Further, we observed no significant impact on ADSC viability. We cocultured fluorescently labeled GBM cells with myxoma virus-infected ADSCs in three- dimensional assay and observed successful cross infection and concomitant cell death almost exclusively in GBM cells. In vivo orthotopic studies injected with vMyxgfp-ADSCs intracranially away from the tumor demonstrated that myxoma virus was delivered by ADSCs resulting in significant survival increase. Our data suggest that ADSCs are promising new carriers of oncolytic viruses, specifically myxoma virus, to brain tumors.