Antigen-mediated migration of murine pro-B Ba/F3 cells via an antibody/receptor chimera
Antigen-mediated migration of murine pro-B Ba/F3 cells via an antibody/receptor chimera
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DOI：
10.1016/j.jbiotec.2007.09.009
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发表时间：
2008-01-01
影响因子：
4.1
通讯作者：
Nagamune, Teruyuki
中科院分区：
文献类型：
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作者：
Kawahara, Masahiro;Shimo, Yusuke;Nagamune, Teruyuki
细胞迁移是控制机体发育、稳态和疾病的基本细胞反应之一。因此，人工控制细胞迁移对于许多疾病的治疗具有很大的希望。在这项研究中，我们开发了一种人工细胞迁移系统的基础上嵌合受体，可以响应人工配体，这是完全不同的天然化学引诱剂。嵌合受体的抗荧光素单链抗体拴到细胞外的D2结构域的促红细胞生成素受体（EpoR）和跨膜/胞质结构域的EpoR，gp 130，白细胞介素-2受体，c-Kit，c-Fms，表皮生长因子受体（EGFR）或胰岛素受体组成的表达在鼠Ba/F3 pro-B细胞系。迁移实验表明，嵌合受体含有c-Kit，c-Fms或EGFR的胞质结构域转导迁移信号，响应荧光素标记的牛血清白蛋白（BSA FL）。此外，基于响应于BSA-FL的细胞迁移，我们成功地从基因转导和未转导的细胞的混合物中选择了遗传修饰的细胞。这项研究首次证明了细胞迁移对人工配体的反应，这种配体与天然化学引诱剂完全不同，这表明其在免疫治疗和组织工程中的潜在应用。(C)2007 Elsevier B. V.保留所有权利。
Cell migration is one of the fundamental cellular responses governing development, homeostasis and disorders of the body. Therefore, artificial control of cell migration holds great promise for the treatment of many diseases. In this study, we developed an artificial cell migration system based on chimeric receptors that can respond to an artificial ligand that is quite different from natural chemoattractants. Chimeric receptors consisting of an anti-fluorescein single-chain Fv tethered to the extracellular D2 domain of erythropoietin receptor (EpoR) and the transmembrane/cytoplasmic domains of EpoR, gp130, interleukin-2 receptor, c-Kit, c-Fms, epidermal growth factor receptor (EGFR) or insulin receptor were expressed in the murine Ba/F3 pro-B cell line. Migration assays revealed that chimeric receptors containing the cytoplasmic domain of c-Kit, c-Fms or EGFR transduced migration signals in response to fluorescein-conjugated bovine serum albumin (BSA-FL). Furthermore, based on the cell migration in response to BSA-FL, we successfully selected genetically modified cells from mixtures of gene-transduced and untransduced cells. This study represents the first demonstration of cell migration in response to an artificial ligand that is quite different from natural chemoattractants, suggesting its potential application to immunotherapies and tissue engineering. (C) 2007 Elsevier B.V. All rights reserved.