2014 Fiscal Year Final Research Report
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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| Keywords | 造血幹細胞 / 造血再生 / PAI-1 |
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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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| Free Research Field |
造血幹細胞
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