Centro de Biotecnologia, Instituto de Pesquisas Energéticas e Nucleares, São Paulo, SP, Brazil.
BMC Biotechnol. 2010 Mar 2;10:19. doi: 10.1186/1472-6750-10-19.
Theracyte is a polytetrafluoroethylene membrane macroencapsulation system designed to induce neovascularization at the tissue interface, protecting the cells from host's immune rejection, thereby circumventing the problem of limited half-life and variation in circulating levels. Endostatin is a potent inhibitor of angiogenesis and tumor growth. Continuous delivery of endostatin improves the efficacy and potency of the antitumoral therapy. The purpose of this study was to determine whether recombinant fibroblasts expressing endostatin encapsulated in Theracyte immunoisolation devices can be used for delivery of this therapeutic protein for treatment of mice bearing B16F10 melanoma and Ehrlich tumors.
Mice were inoculated subcutaneously with melanoma (B16F10 cells) or Ehrlich tumor cells at the foot pads. Treatment began when tumor thickness had reached 0.5 mm, by subcutaneous implantation of 107 recombinant encapsulated or non-encapsulated endostatin producer cells. Similar melanoma growth inhibition was obtained for mice treated with encapsulated or non-encapsulated endostatin-expressing cells. The treatment of mice bearing melanoma tumor with encapsulated endostatin-expressing cells was decreased by 50.0%, whereas a decrease of 56.7% in tumor thickness was obtained for mice treated with non-encapsulated cells. Treatment of Ehrlich tumor-bearing mice with non-encapsulated endostatin-expressing cells reduced tumor thickness by 52.4%, whereas lower tumor growth inhibition was obtained for mice treated with encapsulated endostatin-expressing cells: 24.2%. Encapsulated endostatin-secreting fibroblasts failed to survive until the end of the treatment. However, endostatin release from the devices to the surrounding tissues was confirmed by immunostaining. Decrease in vascular structures, functional vessels and extension of the vascular area were observed in melanoma microenvironments.
This study indicates that immunoisolation devices containing endostatin-expressing cells are effective for the inhibition of the growth of melanoma and Ehrlich tumors.Macroencapsulation of engineered cells is therefore a reliable platform for the refinement of innovative therapeutic strategies against tumors.
Theracyte 是一种聚四氟乙烯膜的宏观封装系统，旨在诱导组织界面的新生血管形成，保护细胞免受宿主的免疫排斥，从而避免半衰期有限和循环水平变化的问题。内皮抑素是一种有效的血管生成和肿瘤生长抑制剂。内皮抑素的持续递送可以提高抗肿瘤治疗的疗效和效力。本研究旨在确定表达内皮抑素的重组成纤维细胞是否可以被封装在 Theracyte 免疫隔离装置中，用于递送这种治疗性蛋白，以治疗携带 B16F10 黑色素瘤和 Ehrlich 肿瘤的小鼠。
将黑色素瘤（B16F10 细胞）或 Ehrlich 肿瘤细胞皮下接种于小鼠足底。当肿瘤厚度达到 0.5mm 时，通过皮下植入 107 个重组的封装或非封装的内皮抑素产生细胞开始治疗。用封装或非封装的表达内皮抑素的细胞治疗的小鼠获得了相似的黑色素瘤生长抑制。用封装的表达内皮抑素的细胞治疗携带黑色素瘤肿瘤的小鼠，肿瘤厚度减少了 50.0%，而用非封装的细胞治疗的小鼠肿瘤厚度减少了 56.7%。用非封装的表达内皮抑素的细胞治疗携带 Ehrlich 肿瘤的小鼠，肿瘤厚度减少了 52.4%，而用封装的表达内皮抑素的细胞治疗的小鼠肿瘤生长抑制率较低：24.2%。封装的表达内皮抑素的成纤维细胞未能存活到治疗结束。然而，通过免疫染色证实了内皮抑素从装置释放到周围组织。在黑色素瘤微环境中观察到血管结构、功能血管和血管面积的扩展减少。
本研究表明，含有表达内皮抑素的细胞的免疫隔离装置可有效抑制黑色素瘤和 Ehrlich 肿瘤的生长。因此，工程细胞的宏观封装是完善针对肿瘤的创新治疗策略的可靠平台。
