The role on bone marrow-derived cells in lung repair and regeneration.

骨髓源性细胞在肺修复和再生中的作用。

• 批准号: 15590792
• 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: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15590792/
• 关键词: regenerative medicine; lung regeneration; pulmonary emphysema; bone marrow-derived cells; stem cells; growth factors; alveolar epithelial cells; capillary endothelial cells

All-trans-retinoic-acid (ATRA) is known to reverse the anatomic and physiologic signs of pulmonary emphysema. However, the origin of the progenitor cells involved in this lung regeneration remains unclear. Recently, it was shown that bone marrow could be the source of progenitor cells for several cell types. Mice with elastase-induced emphysema were treated with ATRA, granulocyte-colony stimulating factor (G-CSF), or a combination of both. ATRA or G-CSF promoted lung regeneration and increased BMC numbers in alveoli. Combined treatment of both had an additive effect, which indicated that BMC mobilization might be important in lung regeneration. In addition, Circulating endothelial progenitor cells (EPCs) play a pivotal role in angiogenesis. Hepatocyte growth factor (HGF) is known to induce proliferation and motility in endothelial cells, and to play a role in mitogenic and morphogenic actions. However, the role of HGF in EPC mobilization has not been dearly described yet. We investigated the effect of HGF on mobilizing EPCs and on angiogenesis in elastase-induced lung injury. HGF significantly increased the triple-positive (Sca-1+, Flk-1+, and c-kit+) fraction in peripheral mononuclear cells in mice. The bone marrow-derived cells were recruited into the injured lungs, where they differentiated to capillary endothelial cells. HGF induced proliferation of both bone marrow-derived and resident endothelial cells in the alveolar wall. In conclusion, the present study suggests that HGF induces EPC mobilization from the bone marrow, and enhances the proliferation of endothelial cells in vivo. These complex effects induced by HGF orchestrate pulmonary regeneration in emphysematous lung parenchyma.

全反式维甲酸（ATRA）被认为可以逆转肺气肿的解剖和生理体征。然而，参与肺再生的祖细胞的起源仍不清楚。最近，研究表明，骨髓可以是几种细胞类型的祖细胞的来源。用ATRA、粒细胞集落刺激因子（G-CSF）或两者联合治疗弹性蛋白酶诱导的肺气肿小鼠。ATRA或G-CSF可促进肺再生，增加肺泡BMC数量。两者联合治疗具有相加效应，这表明BMC动员在肺再生中可能是重要的。此外，循环内皮祖细胞（EPCs）在血管生成中起着关键作用。肝细胞生长因子（HGF）是已知的诱导内皮细胞的增殖和运动，并在有丝分裂和形态发生的行动中发挥作用。然而，HGF在EPC动员中的作用尚未得到详细描述。我们研究了在弹性蛋白酶诱导的肺损伤中HGF对动员EPCs和血管生成的影响。HGF显著增加小鼠外周血单个核细胞中的三重阳性（Sca-1+、Flk-1+和c-kit+）分数。骨髓来源的细胞被招募到受伤的肺中，在那里它们分化为毛细血管内皮细胞。肝细胞生长因子诱导的增殖骨髓来源的和驻地的内皮细胞在肺泡壁。总之，本研究表明HGF诱导骨髓中的EPC动员，并增强体内内皮细胞的增殖。HGF诱导的这些复杂作用协调了肺气肿肺实质的肺再生。

项目成果

Bone marrow-derived cells contribute to lung regeneration after elastase-induced pulmonary emphysema

• DOI: 10.1016/s0014-5793(03)01399-1
• 发表时间: 2004-01-02
• 期刊: FEBS LETTERS
• 影响因子: 3.5
• 作者: Ishizawa, K;Kubo, H;Sasaki, H
• 通讯作者: Sasaki, H

Song C, et al.: "Effects of antiplatelet agents on pulmonary haemodynamic response to fMLP in endotoxin primed rats"Thorax. 59. 39-44 (2004)

Song C 等人：“抗血小板药物对内毒素引发大鼠中 fMLP 肺血流动力学反应的影响”Thorax。

Interferon-γ:: a key contributor to hyperoxia-induced lung injury in mice

• DOI: 10.1152/ajplung.00155.2004
• 发表时间: 2004-11-01
• 期刊: AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
• 影响因子: 4.9
• 作者: Yamada, M;Kubo, H;Sasaki, H
• 通讯作者: Sasaki, H

Hepatocyte growth factor induces angiogenesis in injured lungs through mobilizing endothelial progenitor cells.

• DOI: 10.1016/j.bbrc.2004.09.049
• 发表时间: 2004-11
• 期刊: Biochemical and biophysical research communications
• 影响因子: 3.1
• 作者: Kota Ishizawa;H. Kubo;M. Yamada;Seiichi Kobayashi;Takashi Suzuki;S. Mizuno;Toshikazu Nakamura;Hidetada Sasaki

Effects of antiplatelet agents on pulmonary haemodynamic response to fMLP in endotoxin primed rats.

抗血小板药物对内毒素引发大鼠肺血流动力学对 fMLP 反应的影响。

• 发表时间: 2004
• 期刊: Thorax 59
• 作者: Song C;et al.
• 通讯作者: et al.