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In this review, we examine the applicability of the vascularized bone marrow transplant (VBMT) as an alternative to conventional bone marrow transplantation (BMT). As a new surgical approach, the VBMT is unique by transplantation of the stromal environment that eliminates the need for an engraftment period, provides critical signaling and modulatory functions, and may potentiate tolerance induction. Thus far, VBMT studies have demonstrated an absence of graft-versus-host disease (GVHD) and robust engraftment into nonmanipulated as well as irradiated recipients with evidence of immunological tolerance. Further investigation is needed to determine the applicability of VBMT as an alternative to BMT.

It was demonstrated by Bitter-Seurmann et al. that tolerance to subsequent skin allografts can be brought about, in some rat strain combinations, by heterotopic spleen allografts. We report here that in adult rats, tolerance can be also induced by vascularized spleen allografts using various strain combinations. DA (RT1av1) rats always accepted major histocompatible complex (MHC)-compatible but minor histocompatibility antigen (miH)-incompatible ACI (RT1av1) spleen grafts spontaneously, and further that those DA rats bearing ACI spleen grafts accepted subsequent ACI skin grafts indefinitely. In contrast, Fischer 344 (RT1lvl) rats always accepted not only the "weak" MHC-incompatible Lewis (RT1l) spleen grafts but also subsequent Lewis skin grafts indefinitely, when recipients were administered a short course of FK506 only at the time of primary spleen transplantation. Furthermore, in a number of MHC- and miH-incompatible strain combinations, recipients always accepted primary spleen grafts indefinitely when given a short course of FK506, but those recipients bearing donor spleens revealed split tolerance, that is, rejected subsequent donor-specific skin grafts but accepted heart grafts indefinitely. We conclude that the spleen seems to be a possible organ to induce transplantation tolerance, and that even if the MHC and miH are mismatched, unresponsiveness to at least heart grafts can be achieved by the administration of additional FK506 at the time of spleen transplantation.

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