Development of Regenerative Medicine for COPD

慢阻肺再生医学的发展

• 批准号: 17590774
• 负责人: KUBO Hiroshi
• 金额: $ 2.24万
• 依托单位: Tohoku University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17590774/
• 关键词: Regenerative Medicine; Cell therapy; Respiratory Medicine; Pulmonary emphysema; Stem cell; Differentiation; Lung epithelial cell; Tissue repair; 再生医療; 慢性閉塞性肺疾患

The bone marrow of the C57BL/6 mouse was reconstituted with GFP-transgenic, and the GFP-chimera mouse was made. The acute lung injury was developed by LPS in this chimera mouse, and the lung cells were analyzed by obtaining single cell suspension from the pulmonary tissue after 1, 2 or 6 months of LPS-instillation. FACS analyses were performed using several stem cell markers. As a result, the ratio of the GFP-positive cells in the alveolar walls gradually decreased at the stage of 6 months after acute lung injury. The endogenous stem cells of existing lungs in the chronic phase shows relations in the repair processes after the injury though the bone marrow-derived cell plays a major role at the acute repair period. Moreover, the GFP-positive cells did not exist in the population of lung endogenous stem cells, suggesting that the bone marrow cells were not a source of lung endogenous stem cells. These data suggested that not only the bone marrow-derived cell but also existing endogenous stem cells were important in repair processes of acute lung injury. Then, the role of the lung endogenous stem cells in the lung regeneration model from pulmonary emphysema was examined. The hepatocyte growth factor (HGF)-induced lung regeneration model in the elastase-induced emphysema was utilized for this study. As a result, increasing the number of cell groups with the stem cell markers such as CD34 in the pulmonary tissue was observed, and these cells were necessary for HGF-induced regeneration of the destroyed lungs. Moreover, it was clarified for HGF to increase the number of such lung endogenous stem cells, and to promote the differentiation of these stem cell groups into the mature lungs cells. These results are being in under revision in the Molecular Therapy.

将C57BL/6小鼠的骨髓进行GFP转基因重建，制成GFP嵌合体小鼠。该嵌合体小鼠因LPS而产生急性肺损伤，并通过在LPS滴注1、2或6个月后从肺组织中获取单细胞悬液来分析肺细胞。使用多种干细胞标记物进行 FACS 分析。结果，在急性肺损伤后6个月阶段，肺泡壁中GFP阳性细胞的比例逐渐下降。尽管骨髓源性细胞在急性修复期发挥主要作用，但慢性期现有肺部的内源性干细胞在损伤后的修复过程中显示出相关性。此外，肺内源性干细胞群中不存在GFP阳性细胞，表明骨髓细胞不是肺内源性干细胞的来源。这些数据表明，不仅骨髓来源的细胞，现有的内源性干细胞在急性肺损伤的修复过程中也很重要。然后，检查了肺内源性干细胞在肺气肿肺再生模型中的作用。本研究采用弹性蛋白酶诱导的肺气肿中肝细胞生长因子（HGF）诱导的肺再生模型。结果，观察到肺组织中带有干细胞标记物（例如 CD34）的细胞群数量增加，这些细胞是 HGF 诱导受损肺再生所必需的。此外，还阐明HGF可以增加这种肺内源性干细胞的数量，并促进这些干细胞群分化为成熟的肺细胞。这些结果正在分子疗法中进行修订。

项目成果

Interleukin-1beta gene polymorphisms associated with COPD.

• 发表时间: 2005
• 期刊: Chest
• 影响因子: 9.6
• 作者: M. Asada;M. Yamaya;S. Ebihara;H. Yasuda;Naoki Tomita;H. Kubo;Hidetada Sasaki

Interaction of non-adherent suspended neutrophils to complement opsonized pathogens: a new assay using optical traps.

非粘附悬浮中性粒细胞与调理病原体的相互作用：一种使用光陷阱的新测定。

• 发表时间: 2006
• 期刊: Cell Res 16
• 作者: Suzuki T;et. al.
• 通讯作者: et. al.

Comment on "Cutting Edge: TLR4 deficiency confers susceptibility to lethal oxidant lung injury

对“前沿：TLR4 缺乏导致对致命性氧化性肺损伤的易感性”的评论

• 发表时间: 2006
• 期刊: J immunol 176
• 作者: Kubo H;et al.
• 通讯作者: et al.

The proton pump inhibitor lansoprazole inhibits rhinovirus infection in cultured human tracheal epithelial cells

• DOI: 10.1016/j.ejphar.2004.12.042
• 发表时间: 2005-02-21
• 期刊: EUROPEAN JOURNAL OF PHARMACOLOGY
• 影响因子: 5
• 作者: Sasaki, T;Yamaya, M;Sasaki, H
• 通讯作者: Sasaki, H

最新医学.肺損傷と修復の分子メカニズム.

肺损伤和修复的分子机制。

• 发表时间: 2006
• 作者: Hirama N;Shibata Y;Otake K;Machiya J;Wada T;Inoue S;Abe S;Takabatake N;Sata M;Kubota I;久保裕司
• 通讯作者: 久保裕司