An isolated vascularized bone marrow transplant (iVBMT) model was previously developed in the rat to specifically study the role of bone marrow and its environment in a composite tissue allotransplant. An extraperitoneal model was successfully created to avoid laparotomy and cross-clamping of the great vessels. The extraperitoneal iVBMT model consisted of a left donor femur that was harvested with its nutrient vessels, anastomosed to the right femoral vessels in a syngeneic host, and then placed subcutaneously in the abdominal wall. At explant, the graft vessels were grossly patent, and histology of the graft bones showed a viable marrow compartment. Polymerase chain reaction demonstrated peripheral chimerism in the recipients. This model is technically simple with minimal morbidity in the recipient animals. By using the iVBMT, future studies across semiallogeneic and allogeneic barriers will help define the role of the bone marrow compartment in composite tissue allotransplants to potentially induce immune tolerance.
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.
We describe the largest reported case of pilomatrixoma in the literature. While pilomatrixomas typically present as small soft-tissue nodules of the head, neck and upper extremities, they can also present as much larger masses in atypical locations. When they present in their usual size, pilomatrixomas have typical imaging features and can be correctly diagnosed with imaging studies before histological confirmation. Their clinical and imaging diagnosis become challenging when they are very large, as in our case. A giant pilomatrixoma should also be considered for paediatric patients presenting with a large subcutaneous soft-tissue mass.
In previous rat studies, the use of mixed allogeneic chimerism (MAC) to induce host tolerance to hind limb allografts has resulted in severe graft-versus-host disease (GVHD). The purpose of this study was to determine if immunocompetent cells in bone marrow (BM) and/ or lymph nodes (LNs) of transplanted limbs were responsible for inducing GVHD in mixed chimeric hosts. [ACI + Wistar Furth] chimeric rats received ACI hind limbs that were non-irradiated, irradiated (1050 cGy) or lymphadenectomized. Rejection. GVHD and donor chimerism was assessed. Chimeric hosts rejected none of their limbs. However, hosts of non-irradiated hind limbs succumbed to GVHD 22.4 f 0.8 days after transplantation. In contrast. chimeras that received irradiated or lymphadenectomized ACI hind limbs showed no clinical or histological signs of GVHD at 5 months. We conclude that mixed chimeric hosts are susceptible to GVHD due to the immunocompetent cell load provided by the LNs, not the BM, of hind limb allografts.
Double-barrel vascularized free fibula bone graft can be successfully used as the definitive treatment in refractory cases of distal forearm pseudarthrosis and we believe that our technique can be applied to all cases of pseudarthrosis in other patients with a similar presentation and lesion location.
An isolated vascularized bone marrow transplant (iVBMT) model was developed to study the contribution of the bone marrow component in a composite tissue allograft. We hypothesized that the iVBMT would be functional and cause graft-versus-host disease (GVHD) in a fraction of the recipients. Lewis iVBMT grafts were transplanted to Lewis-Brown Norway recipients. Animals were sacrificed at various times from 1 to 14 weeks. Polymerase chain reaction for microchimerism was performed on the host's marrow. No animals exhibited signs of GVHD at death. Histologic examination of the grafts showed a normal mix of hematopoietic and fatty elements and appeared to be functional. Tissues usually affected-tongue, ear, liver, and gut-also showed no evidence of disease. Polymerase chain reaction demonstrated microchimerism in both groups. These findings suggest that the vascularized bone marrow within a composite tissue allograft is not the component that causes GVHD; rather, it may serve an immunomodulatory function for tolerance induction.
Background
In the nerve allograft model, costimulation blockade has permitted good regeneration but is still inferior to the nerve isograft. We hypothesize that a short course of multiple costimulatory pathway blockade will be more effective in inhibiting the redundancy of the immune response and improve nerve regeneration through the nerve allograft.
Methods
The murine sciatic nerve allograft model was used to reconstruct a 1 cm sciatic nerve gap. Treatment consisted of the inhibition of the CD40, CD28/B7 and ICOS pathways and was compared with only single or double costimulation blockade. Assessment methods included quantitative histomorphometry and ELISPOT assay to quantify the host immune response after 3 weeks post-operatively.
Results
Triple costimulation blockade permitted regeneration through the nerve allograft that was equivalent to the nerve isograft. A short course of three doses was more effective than a single dose for all combinations tested. ELISPOT assay demonstrated minimal in vitro immune response with a short course of double or triple pathway-blocking agents.
Conclusion
Costimulation blockade, especially with the simultaneous inhibition of multiple pathways, remains a promising strategy to promote regeneration through the peripheral nerve allograft, and may be uniquely suited to the temporary immunosuppressive requirements of the peripheral nerve allograft.
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