Medical application of microencapsulating hybridoma cells in agarose microbeads `cytomedicine': therapeutic effect on IgG1 plasmacytosis and mesangio-proliferative glomerulonephritis in the interleukin 6 transgenic mouse
Medical application of microencapsulating hybridoma cells in agarose microbeads `cytomedicine': therapeutic effect on IgG1 plasmacytosis and mesangio-proliferative glomerulonephritis in the interleukin 6 transgenic mouse
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琼脂糖微珠中微囊杂交瘤细胞“细胞医学”的医学应用：对白细胞介素6转基因小鼠IgG1浆细胞增多症和系膜增生性肾小球肾炎的治疗作用
DOI：
10.1016/s0168-3659(96)01522-2
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发表时间：
1997
影响因子：
10.8
通讯作者：
T. Mayumi
中科院分区：
文献类型：
--
作者：
N. Okada;H. Miyamoto;Y. Kaneda;Yoko Yamamoto;A. Katsume;H. Saito;K. Yorozu;O. Ueda;Y. Tsutsumi;S. Nakagawa;Y. Ohsugi;T. Mayumi
我们进行了初步研究，以检验使用微囊活细胞作为生物活性药物（“细胞医学”）载体的可行性，以检验我们的假设，即这种新型药物递送系统作为体内激素、酶和其他生物分子的长期递送系统具有一定的优势。由于活细胞植入同种异体或异种受体时会发生移植排斥反应，因此我们使用琼脂糖微囊技术来防止宿主免疫系统对植入细胞的破坏。人白细胞介素 6 (hIL-6) 转基因小鼠随着年龄的增长会出现大量 IgG1 浆细胞增多症和系膜增生性肾小球肾炎，腹膜内注射含有 SK2 杂交瘤细胞 (SK2 细胞) 的琼脂糖微珠，SK2 杂交瘤细胞可分泌抗 hIL-6 单克隆抗体。这些小鼠表现出治疗反应，IgG1 浆细胞增多和蛋白尿减少，与未治疗组相比，它们的生存时间也延长。这些结果令人鼓舞，表明细胞医学作为生物活性药物体内有效的长期递送系统具有潜在的应用前景。
We conducted preliminary studies to examine the feasibility of using microencapsulated living cells as carriers of bioactive drugs (`cytomedicine') to test our premise that such a novel drug delivery system would have certain advantages as a long-term delivery system for hormones, enzymes and other biomolecules in vivo. As graft rejection occurs when living cells are implanted in allogeneic or xenogeneic recipients, accordingly we used agarose microencapsulation technique to prevent destruction of the implanted cells by the host's immune system. Human interleukin 6 (hIL-6) transgenic mice, which develop massive IgG1 plasmacytosis and mesangio-proliferative glomerulonephritis with age, were intraperitoneally injected with agarose microbeads containing SK2 hybridoma cells (SK2 cells), which secrete anti-hIL-6 monoclonal antibodies. These mice demonstrated therapeutic response with reduced IgG1 plasmacytosis and proteinuria, and they also showed prolongation of survival time compared with the untreated group. These results are encouraging evidence that cytomedicine has potential application as an effective long-term delivery system of bioactive drugs in vivo.