Analysis of pathogenesis of congenital bone marrow failure syndrome and establishment of its treatment using human iPS cells
Project/Area Number |
21390321
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Embryonic/Neonatal medicine
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Research Institution | The University of Tokyo |
Principal Investigator |
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Co-Investigator(Kenkyū-buntansha) |
TSUJI Kohichiro 東京大学, 医科学研究所, 准教授 (50179991)
ETO Kouji 京都大学, iPS細胞研究所, 教授 (50286986)
|
Project Period (FY) |
2009 – 2011
|
Project Status |
Completed (Fiscal Year 2011)
|
Budget Amount *help |
¥18,070,000 (Direct Cost: ¥13,900,000、Indirect Cost: ¥4,170,000)
Fiscal Year 2011: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2010: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2009: ¥7,670,000 (Direct Cost: ¥5,900,000、Indirect Cost: ¥1,770,000)
|
Keywords | iPS細胞 / 先天性骨髄不全症候群 / 重症先天性好中球減少症 / ダウン症候群 / RUNX1 / WNT3a / 好中球 / 巨核球 / 赤血球 / Fanconi貧血 / Kostmann症候群 / Down症候群 |
Research Abstract |
1) Analysis of severe congenital neutropenia-derived iPS cells(SCN-iPS cells) Clonal hematopoietic assay indicated that SCN-iPS cells had a significantly decreased capability to generate neutrophil colonies, which contained few mature neutrophils, reflecting the feature of SCN. Since the expression of WNT/b-Catenin pathway-related genes were decreased, we added WNT3a to hematopoiesis-indunction culture. WNT3a stimulated the maturation of SCN-iPS cell-derived neutrophils. These results suggested the possibility of treatment of SCN using WNT3a. 2) Analysis of Down syndrome-derived iPS cells(DS-iPS cells) Clonal hematopoietic assay indicated that DS-iPS cells had increased capabilities to generate all types of definitive hematopoietic/blood cells. Microarray analysis also demonstrated an increased expression of RUNX1 on chromosome 21, which was confirmed by RT-PCR. These results indicated that hematopoietic abnormalities in DS patients might relate with the increased expression of RUNX1, which could be a target gene for the treatment of hematopoietic disorders in patients with Down syndrome.
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Report
(4 results)
Research Products
(180 results)
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[Journal Article] Integrin αvβ3 regulates thrombopoietin-mediated maintenance of hematopoietic stem cells2012
Author(s)
Umemoto T, Yamato M, Ishihara J, Shiratsuchi Y, Utsumi M, Morita Y, Tsukui H, Terasawa M, Shibata T, Nishida K, Kobayashi Y, Petrich BG, Nakauchi H, Eto K, Okano T
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Journal Title
Blood
Volume: 119(1)
Issue: 1
Pages: 83-94
DOI
Related Report
Peer Reviewed
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[Journal Article] Heterozygous ITGA2B R995W mutation inducing constitutive activation of the {alpha}IIb{beta}3 receptor affects proplatelet formation and causes congenital macrothrombocytopenia2011
Author(s)
Kunishima S, Kashiwagi H, Otsu M, Takayama N, Eto K, Onodera M, Miyajima Y, Takamatsu Y, Suzumiya J, Matsubara K, Tomiyama Y, Saito H
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Journal Title
Blood
Volume: 117
Issue: 20
Pages: 5479-5484
DOI
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Peer Reviewed
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[Journal Article]2010
Author(s)
江藤浩之、高山直也、西村智
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Journal Title
iPS細胞からの血小板への分化誘導と新しい輸血システムの開発【実験医学増刊 再生医療の最前線2010「第3章 幹細胞の分化誘導と臨床応用」】(羊土社)
Pages: 217-222
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[Journal Article] CD8+ effector T cells contribute to macrophage recruitment and adipose tissue inflammation in obesity.2009
Author(s)
Nishimura S, Manabe I, Nagasaki M, Eto K, Yamashita H, Ohsugi M, Otsu M, Hara K, Sugiura S, Yoshimura K, Kadowaki T, Nagai R
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Journal Title
Nature Medicine 15
Pages: 914-920
Related Report
Peer Reviewed
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[Journal Article]2009
Author(s)
海老原康博
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Journal Title
小児がん.がん患者の心に寄り添うためのサイコオンコロジーの基礎と実践. 大木桃代編(真興交易医書出版部)
Pages: 43-47
Related Report
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[Journal Article]2009
Author(s)
江藤浩之
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Journal Title
ES・iPS細胞の有用性に着目した血小板輸血法の開発-献血のいらない血小板製剤への挑戦(医学のあゆみ)
Pages: 495-496
Related Report
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[Journal Article]2009
Author(s)
江藤浩之
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Journal Title
ES細胞およびiPS細胞からの血小板産生【出血性疾患:診断と治療の進歩】(日本内科学会雑誌)
Pages: 119-126
Related Report
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[Journal Article]2009
Author(s)
江藤浩之、中内啓光
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Journal Title
ES細胞由来血小板【治療学「再生医療の細胞ソース3」】(ライフサイエンス社)
Pages: 609-614
Related Report
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[Journal Article]2009
Author(s)
江藤浩之、高山直也、中内啓光
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Journal Title
ES細胞・iPS細胞からの血液細胞の分化誘導-献血に頼らない血小板輸血の実現-【幹細胞の分化誘導と応用「第4編 幹細胞の分化誘導と移植技術」】(NTS社)
Pages: 159-167
Related Report
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[Journal Article]2009
Author(s)
江藤浩之、西村智
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Journal Title
iPS細胞からの血小板産生技術とその方向性【血液フロンティア「再生医療の現状と進歩」】(医薬ジャーナル社)
Pages: 1693-1699
Related Report
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[Journal Article]2009
Author(s)
江藤浩之、高山直也、中内啓光
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Journal Title
iPS細胞からの血小板産生【別冊新しい診断と治療のABC「血小板減少症・増加症」】(最新医学社)
Pages: 182-189
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[Presentation] 慢性骨髄性白血病に対する骨髄破壊的前処置を用いた臍帯血移植2010
Author(s)
河北敏郎, 大井淳, 高橋聡, 塚田信弘, 加藤せい子, 佐藤亜紀, 永田泰之, 海老原康博, 辻浩一郎, 浅野茂隆, 東條有伸
Organizer
第32回日本造血細胞移植学会
Place of Presentation
浜松
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[Presentation] Second or third myeloablative allo-SCT using cord blood for adult leukemia.2009
Author(s)
Kato S, Ooi J, Tahashi S, Tsukada N, Sato A, Konuma T, Kawakita T, Nagata Y, Ebihara Y, Tsuji K, Tojo A, Asano S.
Organizer
第71回日本血液学会総会
Place of Presentation
京都
Related Report
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[Presentation] Definitive Proof for Direct Reprogramming of Hematopoietic Cells to Pluripotency2009
Author(s)
Okabe M, Otsu M, Ahn D H, Kobayashi T, Morita Y, Wakiyama Y, Onodera M, Eto K, Ema H, Nakauchi H
Organizer
International Society for Stem Cell Research 7th AnnuISSCR 7th annual Meeting
Place of Presentation
Barcelona, Spain
Related Report
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[Presentation] CD61/ Integrin β3 Ligation Contributes to the Thrombopoietin-Mediated Niche Function of Mouse Hematopoietic Stem Cells2009
Author(s)
Umemoto T, Yamato M, Shiratsune Y, Tsukada K, Utsumi M, Morita Y, Terasawa M, Shibata T, Nishida K, Kobayashi Y, Petrich GB, Ginsberg MH, Nakauchi H, Eto , Okano. T
Organizer
International Society for Stem Cell Research 7th Annu51th American Society of Hematology
Place of Presentation
New Orleans, USA
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