並列タイトル等カイコまたは昆虫細胞内で生産した細胞増殖因子内包化多角体結晶の有用性に関する研究
一般注記type:Thesis
In clinical settings, medications containing growth factors currently suffer problems with safety and cost because they require high doses and repeated administration over long or short periods due to the short half-life of the growth factors. To address these issues, polyhedra microcrystals derived from the insect-infecting cypovirus 1 within the Reoviridae family were developed. Such polyhedra can be used as vehicles to protect and release encapsulated cell growth factors. As described in Chapter 2, I successfully produced nerve growth factor (NGF)-encapsulating polyhedra (pNGF). These were spotted onto a coverslip to create a uniform circular field; the alignment of differentiated rat neuronal precursor cells (PC12 cells) via their extended axons along the periphery of the pNGF circular field was observed. In addition, I attempted to elucidate the mechanism of cytokine release from polyhedra by investigating whether matrix metalloproteinases (MMPs) secreted from mammalian cells degrade polyhedra. I found that the release of NGF from pNGF was promoted by MMPs secreted from PC12 cells. To date, polyhedra have been produced in baculovirus-infected Spodoptera frugiperda IPLB-SF21-AE cells (Sf21 cells); however, for the purposes of safe medical use in humans, polyhedra should be produced in a virus-free and serum-free system. To produce recombinant polyhedra in such a system, I attempted to generate transgenic silkworms that express target protein-encapsulating polyhedra in their silk glands, which are known to produce fibroin biopolymer (a highly biodegradable and biocompatible material). As detailed in Chapter 3, I generated transgenic silkworm that expresses FGF-7-encapsulating polyhedra (pFGF-7) in their middle and posterior silk glands. Continuous FGF-7 release from the processed posterior silk gland expressing pFGF-7 induced keratinocyte proliferation and enabled the construction of a human epidermal model. The results demonstrate that cytokine-encapsulating polyhedra produced from insect cell lines and individual silkworms could have valuable applications in cell/tissue engineering in vivo and in vitro.
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