Hematopoietic Stem Cell Engraftment and Seeding Permits Multi-Lymphoid Chimerism in Vascularized Bone Marrow Transplants

Abstract

Vascularized bone marrow transplantation (VBMT) across a MHC barrier under a 7-day alphabeta-TCR mAb and CsA protocol facilitated multiple hematolymphoid chimerism via trafficking of the immature (CD90) bone marrow cells (BMC) between donor and recipient compartments. Early engraftment of donor BMC [BN(RT1(n))] into the recipient BM compartment [LEW(RT1(l))] was achieved at 1 week posttransplant and this was associated with active hematopoiesis within allografted bone and correlated with high chimerism in the hematolymphoid organs. Two-way trafficking between donor and recipient BM compartments was confirmed by the presence of recipient MHC class I cells (RT1(l)) within the allografted bone up to 3 weeks posttransplant. At 10 weeks posttransplant, decline of BMC viability in allografted bone corresponded with bone fibrosis and lack of hematopoiesis. In contrast, active hematopoiesis was present in the recipient bone as evidenced by the presence of donor-specific immature (CD90/RT1(n)) cells, which correlated with chimerism maintenance. Clonogenic activity of donor-origin cells (RT1(n)) engrafted into the host BM compartment was confirmed by colony-forming units (CFU) assay. These results confirm that hematolymphoid chimerism is developed early post-VBMT by T-cell lineage and despite allografted bone fibrosis chimerism maintenance is supported by B-cell linage and active hematopoiesis of donor-origin cells in the host BM compartment.