2003 Fiscal Year Final Research Report Summary
Functional potential of hematopoietli stem cells In liver development and self-repair of injured liver
| Project/Area Number |
14570980
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Hematology
|
|---|
| Research Institution | Tottori University |
|---|
Principal Investigator |
TAJIMA Fumihito Tottori University, Tottori University hospital, lecturer, 医学部附属病院, 講師 (60335528)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
SHIOTA Goshi Tottori University, Graduate School, Professor, 大学院・医学系研究科, 教授 (70263457)
|
|---|
| Project Period (FY) |
2002 – 2003
|
| Keywords | CD34 / hematopoietic stem cells / granulocyte-colony stimulating factor / retrorsine / CCL / green fluorescent protein / hepatic injury / self repair |
|---|
| Research Abstract |
CD34 expression is alteration by condition of hematopoietic stem cells (HSC). And we demonstrated HSC mobilization from bone marrow (BM) to peripheral blood (PB) via disruption between c-kit and SCF as the mechanism. However, it was not known that PB cells mobilized by granulocyte-colony stimulating factor (G-CSF) can differentiate Into hepatocytes. We tested the hypothesis by transplanting a clonal population of PB cell mobilized by G-CSF and HSC in BM can be mobilized into hepatic injury to induce to repopulate hepatocytes. C57BL6 female-mice were conditioned with intraperitoneal retrorsine injection and CCL before PB transplantation. We prepared single lineage-Sca-1+ c-kit+ CD34+ PB cell sorted from transgenic enhanced green fluorescent protein (EGFP) male-mice injected with G-CSF. And then we transplanted single PB Into the each mouse with hepatic injury through spleen. Markers for Y chromosome, GFP-antigen were used to identify liver cells of PB origin. Liver was examined 2 months later. Single Lin-Sca-1+ c-kit+ CD34+ PB cell from G-CSF-treated mice generated liver cells. In the next experiment, we first transplanted single Lin-Sca-1+ c-kit+ CD34-BM cell from EGFP male donor mice into lethally irradiated B6 female mice. Two months later, transplanted single EGFP+ HSC reconstituted hematopoiesis. The mice were treated with retrorsine-CCL protocol and finally G-CSF was administered. EGFP+ HSC in BM were recruited to the injured liver by G-CSF and generated liver cells. These data demonstrate that G-CSF can mobilize HSC from BM into PB without losing the capability to differentiate to liver cells and strongly suggest that HSC alone have capacity to effect the self-repair of injured livers.
|
