| Project/Area Number |
18K16538
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 55060:Emergency medicine-related
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| Research Institution | Osaka University |
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Principal Investigator |
Umemura Yutaka 大阪大学, 医学系研究科, 招へい教員 (20743561)
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| Project Period (FY) |
2018-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 敗血症 / 幹細胞移植 / 全身炎症反応 / 多臓器障害 / 血管内皮障害 / 血管内皮 / 全身性炎症反応 / 骨髄移植 / 救急医学 |
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| Outline of Final Research Achievements |
The 7-day survival rate significantly improved in the CLP-BMMNCs group compared to the control group (P<0.05). BMMNCs Transplantation significantly suppressed serum levels of pro-inflammatory mediators, such as tumor necrosis factor-alpha, interleukin-6 and histone H3 at 3, 6, and 12 h after CLP. In the BMMNCs group, serum syndecan-1 levels, a main component of the vascular endothelial glycocalyx layer, were significantly lower than those in the control group at 6 h after CLP. Histological analysis revealed edema of the alveolar septum and pulmonary vascular endothelial injury in the control group 6 h after CLP, whereas the morphological alteration was ameliorated in the CLP-BMMNCs group. Ultrastructural analysis of lung vascular endothelial glycocalyx was performed by using scanning electron microscopic (SEM) with lanthanum nitrate staining. Shedding of vascular endothelial glycocalyx improved in the CLP-BMMNCs group.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究の結果より、BMMNCs投与により血管内皮のグリコカリックス層の保護を介して、敗血症による全身性炎症反応、遠隔臓器障害が抑制され、生命転帰の改善につながる可能性が示唆された。BMMNCsが敗血症などの急性炎症病態に対して有効性を発揮するメカニズムの一端を解明したことで、本治療法の臨床応用を進めていくための礎を築くことができた。今後、BMMNCs投与の有用性と安全性が臨床的に確立されれば、敗血症診療の成績を劇的に向上させる可能性がある。
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