Maintenance of donor-specific chimerism despite osteopontin-associated bone fibrosis in a vascularized bone marrow transplantation model.

Background: The role of vascularized bone allografting is not established in plastic and reconstructive surgery. The authors evaluated the contribution by osteopontin to fibrosis of allografted bone in a vascularized bone marrow transplantation model across a major histocompatibility complex barrier. Methods: Thirty-six transplantations were performed between Brown Norway (RT1 n ) donors and Lewis (RT1 1 ) recipients divided into three groups: group 1, isografts between Lewis rats (n = 12); group 2, allografts without treatment (n = 8); and group 3, allografts under a 7-day αβ-T-cell receptor/cyclosporine protocol (n = 16). Flow cytometry assessed the presence of chimerism for donor major histocompatibility complex class I (RT1 n ) antigens. Immunostaining was used to determine osteopontin expression in grafted and recipient bone, and histologic examination was used to assess bone architecture. Results: Early engraftment of donor bone marrow cells (RT1 n ) into the recipient bone marrow compartment was achieved at posttransplantation day 7. This corresponded with osteopontin expression restricted to the endosteum of trabecular bone and was associated with the preservation of hematopoietic cells within donor bone. Cell migration between donor and recipient bone marrow compartments was confirmed by the presence of recipient cells (RT1 1 ) within the allografted bone and donor-origin cells (RT1 n ) within the recipient bone. At posttransplantation day 63, osteopontin expression within allografted bone was associated with allograft bone fibrosis and lack of hematopoietic properties. In contrast, the recipient's contralateral bone demonstrated a highly localized osteopontin expression pattern within the endosteum and active hematopoiesis with the presence of donor-specific (RT1 n ) cells and correlated with chimerism maintenance. Conclusions: These results confirm that despite up-regulation of osteopontin expression and fibrosis of allografted bone, vascularized bone marrow transplantation resulted in efficient engraftment of donor cells into the recipient's bone marrow compartment, leading to chimerism maintenance.