| Project/Area Number |
17590714
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Circulatory organs internal medicine
|
|---|
| Research Institution | Niigata University |
|---|
Principal Investigator |
TOBA Ken Niigata University, Medical and Dental Hospital, Lecturer, 医歯学総合病院, 講師 (60313540)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
KATO Kiminori Niigata University, Medical and Dental Hospital, Assistant, 医歯学総合病院, 助手 (00303165)
HANAWA Haruo Niigata University, Institute of Medicine and Dentistry, Lecturer, 医歯学系, 講師 (40282983)
AIZAWA Yoshifusa Niigata University, Institute of Medicine and Dentistry, Professor, 医歯学系, 教授 (50143780)
|
|---|
| Project Period (FY) |
2005 – 2006
|
| Project Status |
Completed (Fiscal Year 2006)
|
| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2006: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2005: ¥3,000,000 (Direct Cost: ¥3,000,000)
|
|---|
| Keywords | Angiogenesis / Erythroblasts / Erythropoietin / Ex vivo expansion / Cell Therapy |
|---|
| Research Abstract |
Autologous bone marrow cell implantation (BMI) has been utilized for the treatment of limb ischemia, however the mechanism of angiogenesis by the therapy is not well known. As large as 500 to 1,000 mL of bone marrow collection is usually required for the treatment. The aim of this study was to develop a sophisticated cell therapy by using ex vivo cell culture technique.
In the beginning, we studied the mechanism of angiogenesis by BMI. We expected that the angiogenesis by the therapy mimicked the constitutional angiogenesis in the bone marrow tissue. Several angiogenic factors were strongly produced by erythroblasts. In vitro angiogenesis of HUVEC was conducted by erythroid colonies but not by myeloid colonies prepared from human blood stem cells. Erythroid cells in bone marrow played essential roles for angiogenesis in mouse limb ischemia model. In the in vivo model, simultaneous administration of erythropoietin with BMI enhanced angiogenesis presumably through surviving effect on erythroid cells extramedullary.
Next, we developed an ex vivo expansion system of erythroid cells from bone marrow stem cells. As the results, only 1 mL of bone marrow was enough to produce angiogenic factor producing cells that were fully compatible with 500 to 1,000 mL of freshly harvested bone marrow. The ex vivo expanded erythroblasts also expressed strong angiogenic effect in the mouse limb ischemic model.
A phase I/II trial of "Ex vivo expanded autologous erythroblast transplantation for the treatment of the patients with limb ischemia (EVEETA)" has been approved by the ethical committee and the IRB in the hospital. Cell culture for the clinical use will be enforced in the GMP-grade Cell Processing Center (CPC) in the hospital.
|
