| Project/Area Number |
24591434
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Research Field |
Hematology
|
|---|
| Research Institution | Hyogo Medical University |
|---|
Principal Investigator |
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
OKADA Masaya 兵庫医科大学, 医学部, 講師 (00309452)
KAIDA Katuzi 兵庫医科大学, 医学部, 助教 (00441254)
IKEGAME Kazuhiro 兵庫医科大学, 医学部, 講師 (20372609)
INOUE Takayuki 兵庫医科大学, 医学部, 助教 (20441256)
|
|---|
| Project Period (FY) |
2012-04-01 – 2015-03-31
|
| Project Status |
Completed (Fiscal Year 2014)
|
| Budget Amount *help |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
|
|---|
| Keywords | 造血幹細胞移植 / HLA半合致移植 / 移植片対宿主病 / 可溶性IL-2受容体 / 白血病 / 制御性T細胞 / 移植片対白血病効果 / 同種骨髄移植 / GVL / GVHD |
|---|
| Outline of Final Research Achievements |
We developed a new regimen for unmanipulated HLA-haploidentical stem cell transplantation using reduced intensity conditioning, low dose of anti-thymocyte globulin and steroids. As graft-versus-host disease is a major drawback in haploidentical transplantation, we found that soluble interleukin-2 receptor level on day 7 was important as a predictor of graft-versus-host disease. In a prospective multicenter trial, the rate of donor engraftment and survival on day 100 was 100% and 88.2%, respectively. These data showed that this regimen was safe and feasible.
To study cellular mechanisms of haploidentical transplantation, we independently developed a murine MHC-haploidentical stem cell transplantation model, and studied the kinetics of immune cells in mesenteric lymph nodes early in transplantation. As a result, host-derived regulatory T cells were found to negatively regulate host dendritic cells, resulting in inducing the tolerance between donor and recipients.
|
