Purpose:
This study was designed to evaluate the efficacy of different routes of BMC transplantation on development of donor specific chimerism across major histocompatibility complex barrier under 7-day alpha-beta-TCR/CsA treatment protocol.
Methods:
Thirty two BMC transplantations were performed between ACI (RT1a) donors and Lewis (RT11) recipients. In 8 groups (n=4 of each group) each receiving 100x10 6 BMC, following BMC delivery routes included: intravenous (Groups 1 and 2), intraosseus (Groups 3 and 4), renal intra-capsular (Groups 5 and 6) and intra-testicular (Groups 7 and 8). Groups 1,3,5,7 (controls) received BMC transplantation without immunosuppression, whereas groups 2,4,6,8 received BMC transplantation under 7 day alpha-beta-TCR/CsA protocol. Flow cytometry monitored immunodepletion and donor specific chimerism for MHC class I for T-cells, B-cells and monocyte/granulocyte antigens.
Results:
All animals survived without development of graft-versus-host disease up to 35 days. In summary: As early as 7 day post-transplant in intra-testicular and renal intra-capsular transplanted groups under alpha-beta-TCR/CsA therapy, chimerism was supported predominantly by T-cells, and monocyte/granulocyte populations. During follow-up period at day 35 post-transplant, chimerism declined in all transplanted groups. In treatment groups chimerism decreased by 49% after intravenous, 22% after intraosseus, 78% after intracapsular, and 85% after intra-testicular BMC delivery.
Despite the fact that the highest level of chimerism decline was found after intra-testicular and intra-capsular BMC transplantation, total level of chimerism was still superior compared to intraosseus and intravenous BMC transplantation, and was assessed as follows: 13.27% (intra-testicular), 22.71% (intra-capsular), 11.46% (intraosseus), 7.49% (intravenous) respectively.
All animals are still under observation in good condition and long-term results also will be presented.
Conclusion:
Our observations indicate that chimerism induction and maintenance is superior when BMC is delivered into privileged environment (intraosseus) or to barrier carrying organ such as renal intra-capsular and intra-testicular BMC delivery compared to standard intravenous injection. This study has proven that BMC transplantation into immuno-privileged compartment may be a preferred method of transplantation and currently studies are carried out testing its efficacy in composite tissue transplantation models.