2019 Fiscal Year Final Research Report
Adipose-tissue derived mesenchymal stromal cells containing nanoparticles conjugated with statin for treatment of pulmonary arterial hypertension
| Project/Area Number |
17K10163
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Pediatrics
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| Research Institution | Osaka Medical College |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
伊井 正明 大阪医科大学, 研究支援センター, 講師 (10442922)
岸 勘太 大阪医科大学, 医学部, 特別職務担当教員(助教) (20408503)
小西 隼人 大阪医科大学, 医学部, 助教 (40821814)
島田 亮 大阪医科大学, 医学部, 助教 (60795079)
永塚 健宏 大阪医科大学, 研究支援センター, 特別職務担当教員(助教) (10860083)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Keywords | 先天性心疾患 / 肺動脈性高血圧 / 脂肪組織由来間葉系幹細胞 / スタチン / 再生医療 |
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| Outline of Final Research Achievements |
Congenital heart disease often causes pulmonary arterial hypertension (PAH) resulting to life-threatening events. The major pathological finding of PAH is severe lumen narrowing by medial smooth muscle hypertrophy and neointimal hyperplasia in the pulmonary arterioles (PA). We hypothesized that adipose-tissue derived mesenchymal stromal cell (AdSCs) with the pleiotropic effects of a statin (simvastatin) could ameliorate the impaired vascular lesions and relating RV hypertrophy leading to heart failure. Murine AdSCs containing nanoparticles conjugated with simvastatin (sim-AdSCs) were prepared and intravenously injected into the VEGF-inhibition/hypoxia-induced PAH mouse. The sim-AdSCs significantly reduced the increased RV pressure and RV mass, compared to vehicle or AdSCs alone. In addition, the sim-AdSCs significantly suppressed the proliferation of the rat PA smooth muscle cells in vitro. Taken together, the sim-AdSCs would be a possible new therapeutic option of PAH.
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| Free Research Field |
医学
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| Academic Significance and Societal Importance of the Research Achievements |
PAHに対する薬物治療は進化したもののその効果は残存血管の機能保持に留まり、病変を正常化させる治癒効果はない。スタチン抱合AdSC投与がこの課題を解決する可能性を科学的に示された。実用化までには、更なるコンセプト検証、安全性検討、製造体制、そして臨床試験などの多くのステップを乗り越える必要があるものの、PAHの治療に再生医療の応用が選択肢になる可能性が示唆された。
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