| First Author | Imado T | Year | 2004 |
| Journal | Blood | Volume | 104 |
| Issue | 5 | Pages | 1542-9 |
| PubMed ID | 15100150 | Mgi Jnum | J:90346 |
| Mgi Id | MGI:3043176 | Doi | 10.1182/blood-2003-12-4309 |
| Citation | Imado T, et al. (2004) Hepatocyte growth factor preserves graft-versus-leukemia effect and T-cell reconstitution after marrow transplantation. Blood 104(5):1542-9 |
| abstractText | Graft-versus-host disease (GVHD) is a major complication of allogeneic bone marrow transplantation (BMT). When GVHD is controlled by T-cell-depleted grafts or immunosuppressants, BM transplant recipients often suffer from an increased rate of leukemic relapse and impaired reconstitution of immunity. Using a mouse BMT model, we investigated the effects of hepatocyte growth factor (HGF) gene transfection on the severity of GVHD, the graft-versus-leukemia effect, and the reconstitution of T cells after BMT. After HGF gene transfer, acute GVHD was reduced, while mature donor T-cell responses to host antigens were preserved, resulting in a significant improvement of leukemia-free survival. HGF gene transfer promoted regeneration of bone marrow-derived T cells and the responsiveness of these cells to alloantigens. Furthermore, HGF preserved the thymocyte phenotype and thymic stromal architecture in mice with GVHD. This suggested that HGF exerts a potent protective effect on the thymus, which in turn promotes reconstitution of bone marrow-derived T cells after allogeneic BMT. These results indicate that HGF gene transfection can reduce acute GVHD preserving the graft-versus-leukemia effect, while promoting thymic-dependent T-cell reconstitution after allogeneic BMT. |
