Continuous release of endostatin from microencapsulated engineered cells for tumor therapy
Continuous release of endostatin from microencapsulated engineered cells for tumor therapy
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DOI：
10.1038/83481
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发表时间：
2001-01-01
影响因子：
46.9
通讯作者：
Black, PM
中科院分区：
文献类型：
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作者：
Joki, T;Machluf, M;Black, PM
研究表明，肿瘤相关的血管生成有助于恶性胶质瘤的表型。我们评估了局部递送血管生成抑制剂内皮抑素对人胶质瘤细胞系（U-87 MG）异种移植物的影响。用人内皮抑制素（hES）表达载体稳定转染幼仓鼠肾（BHK）细胞，并将其包封在藻酸盐-聚L-赖氨酸（PLL）微胶囊中，用于长期递送hES。使用牛毛细血管内皮细胞（BCE）增殖和管形成的测定来确认生物活性内皮抑素的释放。微囊释放的人内皮抑素对BCE的增殖抑制率为67.2%。此外，分泌的hES能够抑制用条件U-87 MG培养基处理的KDR/PAE细胞（用酪氨酸激酶KDR稳定转染的猪主动脉内皮细胞）中的管形成。在裸鼠模型中单次局部注射包封的内皮抑制素分泌细胞导致治疗后21天皮下U87异种移植物重量减少72.3%。仅通过从2 × 10（5）包封的细胞分泌的150.8 ng/ml人内皮抑制素就实现了这种抑制。包封的内皮抑制素分泌细胞可有效治疗人胶质母细胞瘤异种移植物。内皮抑素的持续局部递送可为治疗各种类型的肿瘤提供有效的治疗方法。
Research studies suggest that tumor-related angiogenesis contributes to the phenotype of malignant gliomas. We assessed the effect of local delivery of the angiogenesis inhibitor endostatin on human glioma cell line (U-87MG) xenografts. Baby hamster kidney (BHK) cells were stably transfected with a human endostatin (hES) expression vector and were encapsulated in alginate-poly L-lysine (PLL) microcapsules for long-term delivery of hES. The release of biologically active endostatin was confirmed using assays of bovine capillary endothelial (BCE) proliferation and of tube formation. Human endostatin released from the microcapsules brought about a 67.2% inhibition of BCE proliferation. Furthermore, secreted hES was able to inhibit tube formation in KDR/PAE cells (porcine aortic endothelial cells stably transfected with KDR, a tyrosine kinase) treated with conditioned U-87MG medium. A single local injection of encapsulated endostatin-secreting cells in a nude mouse model resulted in a 72.3% reduction in subcutaneous U87 xenografts' weight 21 days post treatment. This inhibition was achieved by only 150.8 ng/ml human endostatin secreted from 2 x 10(5) encapsulated cells. Encapsulated endostatin-secreting cells are effective for the treatment of human glioblastoma xenografts. Continuous local delivery of endostatin may offer an effective therapeutic approach to the treatment of a variety of tumor types.