Establishment of hematopoietic regeneration by the novel molecular targeting drug
| Project/Area Number |
24590361
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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 |
General medical chemistry
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| Research Institution | Tokai University |
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Principal Investigator |
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| Co-Investigator(Renkei-kenkyūsha) |
ANDO Kiyoshi 東海大学, 医学部, 教授 (70176014)
MIYATA Toshio 東北大学, 医学系, 教授 (10222332)
IBRAHIM Abd Aziz 東海大学, 医学部, 研究員 (50738789)
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 造血幹細胞 / 造血再生 / PAI-1 / 再生 / 線維素溶解系 / 再生医療 / 低分子化合物 |
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| Outline of Final Research Achievements |
The prognosis of patients undergoing hematopoietic stem cell transplantation depends on the rapid recovery and sustained life-long hematopoiesis. The activation of the fibrinolytic pathway promotes hematopoietic regeneration; however, the role of PAI-1 has not yet been elucidated. We herein demonstrate that BM stromal cells produce PAI-1 in response to myeloablation, which negatively regulates the hematopoietic regeneration. Genetic disruption of the PAI-1 gene, or pharmacological inhibition of PAI-1 activity, significantly improved the myeloablation-related mortality and promoted rapid hematopoietic recovery through the induction of hematopoiesis-promoting factors. The PAI-1 inhibitor not only accelerated the expansion of the donor HSCs during the early stage of regeneration, but also supported long-term hematopoiesis. Our results indicate that the inhibition of PAI-1 activity could be a therapeutic approach to facilitate the rapid recovery and sustained hematopoiesis.
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Report
(4 results)
Research Products
(12 results)
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[Journal Article] Establishment of a humanized APL model via the transplantation of PML-RARA-transduced human common myeloid progenitors into immunodeficient mice2014
Author(s)
Matsushita, H. Yahata, T. Sheng, Y. Nakamura, Y. Muguruma, Y. Matsuzawa, H. Tanaka, M. Hayashi, H. Sato, T. Damdinsuren, A. Onizuka, M. Ito, M. Miyachi, H. Pandolfi, P. P. Ando, K.
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Journal Title
PLoS One
Volume: 9
Issue: 11
Pages: e111082-e111082
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Functional analysis of the SEPT9-ABL1 chimeric fusion gene derived from T-prolymphocytic leukemia.2014
Author(s)
Kawai H, Matsushita H, Suzuki R, Sheng Y, Lu J, Matsuzawa H, Yahata T, Tsuma-Kaneko M, Tsukamoto H, Kawada H, Ogawa Y, Ando K.
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Journal Title
Leukemia Research.
Volume: 38
Issue: 12
Pages: 1451-1559
DOI
Related Report
Peer Reviewed
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[Journal Article] Effective expansion of engrafted human hematopoietic stem cells in bone marrow of mice expressing human Jagged-12014
Author(s)
Negishi, N. Suzuki, D. Ito, R. Irie, N. Matsuo, K. Yahata, T. Nagano, K. Aoki, K. Ohya, K. Hozumi, K. Ando, K. Tamaoki, N. Ito, M. Habu, S.
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Journal Title
Exp Hematol
Volume: 42
Issue: 6
Pages: 487-94
DOI
Related Report
Peer Reviewed
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