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岡本, 駿郎 ; Okamoto, Syunro
概要:
近年は幹細胞を用いた人工神経の研究が進んでいる．今回我々は臨床応用を念頭に置き，脂肪組織由来再生細胞 (adipose derived regenerative cells, ADRCs) を封入した人工神経を作成し，その短期成績について検
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討した．体重2.5 ～3.0kgの日本白色家兎の右側の坐骨神経を切離し，15mmの欠損部を内径3.5mmの管腔物で架橋した．実験群は管腔物，封入物により分類し，I群はシリコンチューブと生理食塩水，II群は人工神経と生理食塩水， III群は人工神経とADRCs，IV群は自家神経移植群とした．各群5羽の計20羽を作成し，肉眼的評価，病理学的評価および電気生理学的評価を行った．肉眼的評価では全例に組織の連続性を認めたが，I群と比較しII，III，IV群では管腔内に組織が充満していた．病理学的評価では，I群と比較しII，III，IV群において髄鞘化の始まった線維像が認められ，特にIV群において顕著であった．また有髄線維数はIV，III，II，I群の順で多くなっており，各群間に有意差を認めた．電気生理学的評価ではIII 群，IV群の成績が良好であったが，各群間には有意差を認めなかった．本研究の結果，ADRCsは神経再生を促進すると考えられ，今後さらに解析を進めることで臨床応用できる可能性があると考えられた．<br />Recently, great progress has been made in the development of stem cell-containing artificial nerve grafts. The present study evaluated the feasibility of an artificial nerve graft containing adipose-derived regenerative cells (ADRCs) for clinical application and examined its short-term results in Japanese white rabbit. In this model, the right sciatic nerve was excised, and a 15 mm gap was bridged by lumen material (3.5 mm). The animals were divided into four groups according to the type of lumen and enclosed material: group I, silicon tube and saline; group II, artificial nerve graft and saline; group III, artificial ner ve graft and ADRCs; and group IV, autologous ner ve graft (n = 5). The macroscopic, pathological, and electrophysiological findings were subsequently evaluated at 4 weeks and 8 weeks postoperatively. The macroscopic findings revealed that the lumina of group I contained less material than those of groups II, III, and IV. The pathological findings indicated a higher prevalence of myelinated fibers in groups II, III, and IV than in group I, which was the most prominent in group IV. The prevalence of myelinated fibers increased in the following order: groups I, II, III, and IV; significant differences were observed among the groups. The electrophysiological findings showed good results in groups III and IV; however, there was no significant difference between groups. The results revealed nerve regeneration by ADRCs. Therefore, the artificial nerve graft containing ADRCs is effective in promoting nerve regeneration, but not as effective as an autologous nerve graft.
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| 2.
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若山, 友彦 ; 塚谷, 才明 ; 三輪, 髙喜 ; 古川, 仭 ; 井関, 尚一
概要:
金沢大学大学院医学系研究科がん細胞学<br />Spermatogenic immunoglobulin superfamily (SgIGSF) is a cell adhesion molecule originally discove
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red in mouse testis. SgIGSF is expressed not only in spermatogenic cells but also in lung and liver epithelial cells and in neurons and glia of the central and peripheral nervous systems. In the present study, we examined the expression and localization of SgIGSF in mouse olfactory epithelium before and after transection of the olfactory nerves, by RT-PCR, Western blotting and immunohistochemistry. In normal olfactory mucosa, SgIGSF showed 100 kDa in molecular weight, which was identical with that in the lung but different from that in the brain. SgIGSF was expressed on the membrane of all olfactory, sustentacular and basal cells, but more abundantly in the apical portions of the olfactory epithelium where the dendrites of olfactory cells are in contact with sustentacular cells. After olfactory nerve transection, mature olfactory cells disappeared in 4 days but were regenerated around 7-15 days by proliferation and differentiation of basal cells into mature olfactory cells through the step of immature olfactory cells. During this period, both the mRNA and protein for SgIGSF showed a transient increase, with peak levels at 7 days and 11 days, respectively, after the transection. Immunohistochemistry showed that the enriched immunoreactivity for SgIGSF at 7-11 days was localized primarily to the membrane of immature olfactory cells. These results suggested that, during regeneration of the olfactory epithelium, the adhesion molecule SgIGSF plays physiological roles in differentiation, migration, and maturation of immature olfactory cells. (C) 2007 The Japan Society of Histochemistry and Cytochemistry.
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Koriyama, Yoshiki ; Yasuda, Rie ; Homma, Keiko ; Mawatari, Kazuhiro ; Nagashima, Mikiko ; Sugitani, Kayo ; Matsukawa, Toru ; Kato, Satoru
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金沢大学医薬保健研究域 医学系<br />Nitric oxide (NO) signaling results in both neurotoxic and neuroprotective effects in CNS and PNS n
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eurons, respectively, after nerve lesioning. We investigated the role of NO signaling on optic nerve regeneration in the goldfish (Carassius auratus). NADPH diaphorase staining revealed that nitric oxide synthase (NOS) activity was up-regulated primarily in the retinal ganglion cells (RGCs) 5-40 days after axotomy. Levels of neuronal NOS (nNOS) mRNA and protein also increased in the RGCs alone during this period. This period (5-40 days) overlapped with the process of axonal elongation during regeneration of the goldfish optic nerve. Therefore, we evaluated the effect of NO signaling molecules upon neurite outgrowth from adult goldfish axotomized RGCs in culture. NO donors and dibutyryl cGMP increased neurite outgrowth dose-dependently. In contrast, a nNOS inhibitor and small interfering RNA, specific for the nNOS gene, suppressed neurite outgrowth from the injured RGCs. Intra-ocular dibutyryl cGMP promoted the axonal regeneration from injured RGCs in vivo. None of these molecules had an effect on cell death/survival in this culture system. This is the first report showing that NO-cGMP signaling pathway through nNOS activation is involved in neuroregeneration in fish CNS neurons after nerve lesioning. © 2009 International Society for Neurochemistry.<br />出版社許諾要件により、2010年9月より全文公開.
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Ogai, Kazuhiro ; Hisano, Suguru ; Sugitani, Kayo ; Koriyama, Yoshiki ; Kato, Satoru
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Zebrafish can regenerate several organs such as the tail fin, heart, central nervous system, and photoreceptors. Very re
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cently, a study has demonstrated the photoreceptor regeneration in the alkylating agent N-methyl-N-nitrosourea (MNU)- induced retinal degeneration (RD) zebrafish model, in which whole photoreceptors are lost within a week after MNU treatment and then regenerated within a month. The research has also shown massive proliferation of Müller cells within a week. To address the question of whether proliferating Müller cells are the source of regenerating photoreceptors, which remains unknown in the MNU-induced zebrafish RD model, we employed a BrdU pulse-chase technique to label the proliferating cells within a week after MNU treatment. As a result of the BrdU pulse-chase technique, a number of BrdU+ cells were observed in the outer nuclear layer as well as the inner nuclear layer. This implies that regenerating photoreceptors are derived from proliferating Müller cells in the zebrafish MNU-induced RD model. © Springer International Publishing Switzerland 2016.<br />[Book Chapter]
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Imamura, Ryu ; Matsumoto, Kunio
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Hepatocyte growth factor (HGF) is a pleiotropic cytokine composed of an α-chain and a β-chain, and these chains contain
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four kringle domains and a serine protease-like structure, respectively. The receptor for HGF was identified as the c-met proto-oncogene product of transmembrane receptor tyrosine kinase. HGF-induced signaling through the receptor Met provokes dynamic biological responses that support morphogenesis, regeneration, and the survival of various cells and tissues, which includes hepatocytes, renal tubular cells, and neurons. Characterization of tissue-specific Met knockout mice has further indicated that the HGF-Met system modulates immune cell functions and also plays an inhibitory role in the progression of chronic inflammation and fibrosis. However, the biological actions that are driven by the HGF-Met pathway all play a role in the acquisition of the malignant characteristics in tumor cells, such as invasion, metastasis, and drug resistance in the tumor microenvironment. Even though oncogenic Met signaling remains the major research focus, the HGF-Met axis has also been implicated in infectious diseases. Many pathogens try to utilize host HGF-Met system to establish comfortable environment for infection. Their strategies are not only simply change the expression level of HGF or Met, but also actively hijack HGF-Met system and deregulating Met signaling using their pathogenic factors. Consequently, the monitoring of HGF and Met expression, along with real-time detection of Met activation, can be a beneficial biomarker of these infectious diseases. Preclinical studies designed to address the therapeutic significance of HGF have been performed on injury/disease models, including acute tissue injury, chronic fibrosis, and cardiovascular and neurodegenerative diseases. Likewise, manipulating the HGF-Met system with complete control will lead to a tailor made treatment for those infectious diseases. © 2016 Elsevier Ltd.<br />Embargo Period 12 months
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Yang, Shi ; Lanchun, Bian
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Under the research framework of changes in morphology, as well as social structure in historic areas in Beijing, this study carries out investigation and quantitative analysis on living space and social and economic problems in
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Shichahai, Xisibei and Nanluoguxiang, and conducts a sample analysis on typical courtyards. Scholars from different fields analyzed issues of social space reconstruction and cultural value protection from the perspectives of political and economic factors and cultural heritage protection and explores strategies for traditional courtyard improvement from the perspectives of physical space and public policy, though the tracking investigation and empirical analysis on the regeneration of traditional courtyards regarding social orientation is quite limited. In this paper the author analyzes social problems existing in physical and social space changes and explored sustainable regeneration strategies for traditional courtyards with social orientation, in Beijing, employing literature research, sampling investigation, participatory observation, in-depth interview and reconnaissance mapping methods.
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松下, 重雄 ; 三橋, 伸夫
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The purpose of this study is to consider characteristics of workings and a future direction of local partnership groups in Japan based on the Groundwork approach in the UK. Compared with Groundwork in the UK, characteristics of
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workings of local Groundwork groups in Japan are summarised as follows: 1) an approach to matters of natural environment in the local community; 2) simple programme contents; 3) a practical activity only by Groundwork group; 4) a vulnerable partnership with the private sector; 5) a support system by volunteer staff with high skill; 6) a low capacity of fund raising and a small fiscal scale; 7) a passive strategy toward government policies. In conclusion, the following four points are necessary for developing Groundwork movement in Japan: 1) a step-by-step approach to enhance social environment; 2) an intermediary to expand a local partnership; 3) an organisational structure composed of full-time staffs with a coordination skill and diversification of finance; 4) a consciousness of a holistic approach strategy.
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