Growth Control of Mammalian Cells via a Human Artificial Chromosome Harboring a Chimeric Receptor

摘要

Cytokines play pivotal roles in controlling cell fate for maintenance of homeostasis in the body. Therefore, mimicry of cytokine functions with artificial ligands is a promising strategy for realizing artificial control of the fates of specific cell populations. To this end, we have designed several antibody/cytokine receptor chimeras that can transduce a growth signal in response to the cognate antigens. An anti-fluorescein single-chain Fv (ScFv) tethered to extracellular D2 domain of the erythropoietin receptor (EpoR) and transmembrane and cytoplasmic domains of gp 130 resulted in marked cell growth promotion in the presence of fluorescein-conjugated BSA (BSA-FL) or a series of fluorescein dimers connected by an oligo-DNA linker in factor-dependent hematopoietic cell lines. This chimeric receptor could be employed to specifically amplify gene-transduced cells in an antigen-dependent manner, a technique known as antigen-mediated genetically modified cell amplification (AMEGA).