Endothelial cell implantation and survival within experimental gliomas.
Endothelial cell implantation and survival within experimental gliomas.
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实验性神经胶质瘤内皮细胞的植入和存活。
DOI：
10.1073/pnas.91.21.9695
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发表时间：
1994
影响因子：
11.1
通讯作者：
Laterra,J
中科院分区：
文献类型：
--
作者：
Lal,B;Indurti,RR;Couraud,PO;Goldstein,GW;Laterra,J
向原发脑肿瘤输送治疗性基因为治疗这些经常致命的肿瘤打开了新的机会。有效的基因转移仍然是治疗的一个重要障碍，由于血-脑和血-肿瘤屏障的存在，这一问题在脑肿瘤中具有独特的特点。实体瘤中内皮细胞有丝分裂原的存在和血管的增殖表明，转基因内皮细胞可能有效地移植到脑瘤中。用腺病毒E1a基因永生化并进一步修饰表达β-半乳糖苷酶报告基因的大鼠脑内皮细胞，检测其移植到实验性大鼠胶质瘤中的存活能力。大鼠接受9L、F98或C6胶质瘤细胞联合内皮细胞尾壳核或皮下至侧翼的移植。植入的内皮细胞通过β-半乳糖苷酶组织化学或聚合酶链式反应在所有肿瘤中进行鉴定，直到移植后35天，最近一次检查。移植的内皮细胞似乎在肿瘤血管形成中协同作用，并表达免疫组织化学鉴定的脑特异性内皮葡萄糖转运体1。移植后14天至21天的肿瘤内内皮细胞数量增加(P=0.015)和增殖抗原Ki67的表达支持了移植内皮细胞的增殖。这些发现证明，转基因内皮细胞可以稳定地移植到生长中的胶质瘤上，并表明内皮细胞移植可能提供了一种向脑肿瘤和其他实体瘤运送治疗性基因的方法。此外，脑内皮细胞移植可能有助于确定脑内皮细胞分化的机制。
The delivery of therapeutic genes to primary brain neoplasms opens new opportunities for treating these frequently fatal tumors. Efficient gene delivery to tissues remains an important obstacle to therapy, and this problem has unique characteristics in brain tumors due to the blood-brain and blood-tumor barriers. The presence of endothelial mitogens and vessel proliferation within solid tumors suggests that genetically modified endothelial cells might efficiently transplant to brain tumors. Rat brain endothelial cells immortalized with the adenovirus E1A gene and further modified to express the beta-galactosidase reporter were examined for their ability to survive implantation to experimental rat gliomas. Rats received 9L, F98, or C6 glioma cells in combination with endothelial cells intracranially to caudate/putamen or subcutaneously to flank. Implanted endothelial cells were identified by beta-galactosidase histochemistry or by polymerase chain reaction in all tumors up to 35 days postimplantation, the latest time examined. Implanted endothelial cells appeared to cooperate in tumor vessel formation and expressed the brain-specific endothelial glucose transporter type 1 as identified by immunohistochemistry. The proliferation of implanted endothelial cells was supported by their increased number within tumors between postimplantation days 14 and 21 (P = 0.015) and by their expression of the proliferation antigen Ki67. These findings establish that genetically modified endothelial cells can be stably engrafted to growing gliomas and suggest that endothelial cell implantation may provide a means of delivering therapeutic genes to brain neoplasms and other solid tumors. In addition, endothelial implantation to brain may be useful for defining mechanisms of brain-specific endothelial differentiation.