| Project/Area Number |
24590361
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Research Field |
General medical chemistry
|
|---|
| Research Institution | Tokai University |
|---|
Principal Investigator |
|
|---|
| 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)
|
|---|
| Project Period (FY) |
2012-04-01 – 2015-03-31
|
| Project Status |
Completed (Fiscal Year 2014)
|
| 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)
|
|---|
| 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 |
|---|
| 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.
|
