New mouse model of rare lung disease and novel therapy with macrophages
Project/Area Number |
16K21750
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Research Category |
Fund for the Promotion of Joint International Research (Home-Returning Researcher Development Research)
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Allocation Type | Multi-year Fund |
Research Field |
Respiratory organ internal medicine
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Research Institution | Jichi Medical University |
Principal Investigator |
SUZUKI Takuji 自治医科大学, 医学部, 准教授 (80344670)
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Project Period (FY) |
2017 – 2019
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Project Status |
Completed (Fiscal Year 2019)
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Budget Amount *help |
¥32,760,000 (Direct Cost: ¥25,200,000、Indirect Cost: ¥7,560,000)
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Keywords | 呼吸器疾患 / 肺胞蛋白症 / ノックアウトマウス / マクロファージ / iPS細胞 |
Outline of Final Research Achievements |
Hereditary pulmonary alveolar proteinosis (hPAP) is rare genetic diseases caused by GM-CSF receptor alpha or beta gene (CSF2RA or CSF2RB, respectively) mutation. hPAP with CSF2RA gene mutation has been difficult to study due to the unavailability of a mouse model with Csf2ra gene mutation. We demonstrated the Csf2ra gene deficient mice are the faithful model of human hPAP with CSF2RA gene mutations. The characteristics of the Csf2ra gene deficient mice including lung histology, macrophage phenotype and function, bronchoalveolar lavage fluid appearance, gene expression profiles and PAP biomarkers showed similar abnormality as hPAP patients with CSF2RA gene mutations. We also demonstrated that pulmonary macrophage transplantation therapy is effective and safe in Csf2ra gene deficient mice. These results strongly support the potential utility of the new disease model mice and the feasibility of novel cell therapy for the patients with this specific genetic lung disease.
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Academic Significance and Societal Importance of the Research Achievements |
これまで存在しなかったヒトCSF2RA遺伝子変異による遺伝性肺胞蛋白症の有効な疾患モデルが確立されたことで、その病態解析および生物学的解析を行えるという学術的意義がある。また、新規治療法の開発といったトランスレーショナルな研究を行うことにより、患者さんへ治療法を還元していくという社会的意義がある。
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Report
(4 results)
Research Products
(26 results)
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[Journal Article] Characteristics of 68 patients with clinically proven sarcoidosis based on the Japan Society of Sarcoidosis and Other Granulomatous Disorders 2015 criteria.2020
Author(s)
Yamanouchi Y, Sawahata M, Sakamoto N, Hisata S, Shijubo N, Konno S, Yamaguchi T, Watanabe M, Kawashima H, Suzuki T, Bando M, Hagiwara K
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Journal Title
Respir Investig.
Volume: 58
Pages: 102-109
Related Report
Peer Reviewed / Open Access
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[Journal Article] Pulmonary Transplantation of Human Induced Pluripotent Stem Cell-derived Macrophages Ameliorates Pulmonary Alveolar Proteinosis.2018
Author(s)
Happle C, Lachmann N, Ackermann M, Mirenska A, Göhring G, Thomay K, Mucci A, Hetzel M, Glomb T, Suzuki T, Chalk C, Glage S, Dittrich-Breiholz O, Trapnell B, Moritz T, Hansen G.
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Journal Title
Am J Respir Crit Care Med.
Volume: 198
Issue: 3
Pages: 350-360
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Statin as a novel pharmacotherapy of pulmonary alveolar proteinosis.2018
Author(s)
McCarthy C, Lee E, Bridges JP, Sallese A, Suzuki T, Woods JC, Bartholmai BJ, Wang T, Chalk C, Carey BC, Arumugam P, Shima K, Tarling EJ, Trapnell BC.
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Journal Title
Nat Commun.
Volume: 9
Issue: 1
Pages: 3127-3127
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] iPSC-Derived Macrophages Effectively Treat Pulmonary Alveolar Proteinosis in Csf2rb-Deficient Mice.2018
Author(s)
Mucci A, Lopez-Rodriguez E, Hetzel M, Liu S, Suzuki T, Happle C, Ackermann M, Kempf H, Hillje R, Kunkiel J, Janosz E, Brennig S, Glage S, Bankstahl JP, Dettmer S, Rodt T, Gohring G, Trapnell B, Hansen G, Trapnell C, Knudsen L, Lachmann N, Moritz T.
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Journal Title
Stem Cell Reports.
Volume: 11
Issue: 3
Pages: 696-710
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Targeting cholesterol homeostasis in lung diseases.2017
Author(s)
Sallese A, Suzuki T, McCarthy C, Bridges J, Filuta A, Arumugam P, Shima K, Ma Y, Wessendarp M, Black D, Chalk C, Carey B, Trapnell BC.
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Journal Title
Scientific Reports
Volume: 7
Issue: 1
Pages: 10211-10211
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Function and Safety of Lentivirus-Mediated Gene Transfer for CSF2RA-Deficiency.2017
Author(s)
Hetzel M**, Suzuki T**, Hashtchin AR, Arumugam P, Carey B, Schwabbauer M, Kuhn A, Meyer J, Schambach A, Van Der Loo J, Moritz T, Trapnell BC, Lachmann N. (** : These authors are equally contributed.)
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Journal Title
Human Gene Therapy Methods
Volume: 28
Issue: 6
Pages: 318-329
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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