2003 Fiscal Year Final Research Report Summary
Establishment of a new model of vascularized bone marrow transplantation : Analyses of immunological tolerance and maintenance
| Project/Area Number |
14571132
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
General surgery
|
|---|
| Research Institution | Hamamatsu University School of Medicine |
|---|
Principal Investigator |
SUZUKI Hidetoshi Hamamatsu University School of Medicine, Second Department of Anatomy, Assistant professor, 医学部, 助手 (70242758)
|
|---|
| Project Period (FY) |
2002 – 2003
|
| Keywords | vascularized bone marrow transplantation / donor-specific immunological tolerance / stem cell transplantation / macrochimerism / organ transplantation |
|---|
| Research Abstract |
Background. The use of hematopoietic stem cells (HSCs) with their environments is one of the promising approaches as a means of creating mixed chimerism, and inducing and maintaining transplantation tolerance. We previously reported a new model of vascular zed femoral bone marrow transplantation (VfBMT) as an organ graft that contained the isolated femoral bone and bone marrow cells (BMCs) with nutrient vessels eliminating other nonparenchimal tissues including skin. Mixed chimerism and immunological tolerance after VfBMT without any pretransplant host conditioning was examined.
Materials and Methods. Fully MHC (Major Histocompatibility Complex)-mismatched male BN (RT1^n) VfBMT were performed microsurgically to Lewis females (RT1^1). Limited Tacrolumus was used for 10 days only after Vfbmt and no pretransplant host conditioning was done before VfBMT. To confirm the level of tolerance subsequent donor-specific BN heart or skin, or simultaneous BN skin grafts with VfBMT were carried out, respectively. Chimerism of donor cells and its phenotypical characteristics were examined by the flwocytoric analysis.
Results. Allogeneic BN VfBMT were indefinitely accepted in Lewis rats only with a short course of tacrolimus. Donor cells persisted for up to 95 weeks in various tissues. Interestingly, myelocytes expressing signal regulatory proteins were predominantly replaced by donor cells. Subsequent donor-specific BN heart grafts were indefinitely accepted on Lewis bearing long-term BN VfBMT. Furthermore, significant prolongation or acceptance more than 100 days of BN skin grafts was confirmed when VfBMT and skin transplantation were simultaneously carried out. While, slight prolongation of survival was shown concerning subsequent BN skin grafts. Conclusion. Induction of unresponsiveness and stable life-long mixed chimerism were achieved by VfBMT without any pretransplant host conditioning.
|
Research Products
(4 results)
