Absence of graft-versus-host disease in the isolated vascularized bone marrow transplant

Abstract

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.

G-CSF Prevents Progression of Diabetic Nephropathy in Rat

“…On the following day, 2×10 8 donor BM cells from male OLETF rats were administered intravenously via the tail vein. Donor BM cells were obtained as described previously [20]. To confirm the DN model, female OLETF rats (after 4 weeks of recovery from BMT; 10 weeks of age) received tap water containing 30% sucrose ad libitum and certified rodent laboratory chow.…”

Tunneled superficial inferior epigastric artery (SIEA) myocutaneous/vascularized femur chimeric flaps: A model to study the role of vascularized bone marrow in composite allografts

“…17,[27][28][29] Additionally, graft-versus-host-disease (GVHD) has not developed following VBM transplantation, supporting the use of VBM contained in composite grafts as an immunomodulatory strategy. 9 The rat combined SIEA myocutaneous/vascularized femur transplant is a promising single-anastomosis model to explore the contributions of VBM to VCA survival, as the VBM component can be either included or excluded without major technical modifications. 12,13 In order to avoid complications of autocannibalization, 30,31 which can complicate clinical and histologic evaluation of rejection, 14 and to facilitate flap monitoring, we sought to further refine the previously described intrinsically chimeric SIEA myocutaneous/vascularized femur model by tunneling the SIEA myocutaneous flap component to the rat dorsum, while maintaining the femoral bone component in a subcutaneous groin pocket.…”

“…[4][5][6] Vascularized bone marrow (VBM) transplantation in particular allows for the uninterrupted transfer of donor bone marrow cells within the preserved donor microenvironment, and is considered to be superior to cellular bone marrow transplantation alone in the induction of tolerance and reduction of immunosuppression requirements. [7][8][9] To evaluate the role of VBM in VCA, the rat superficial inferior epigastric artery (SIEA) free flap, first described by Strauch and Murray in 1967, 10 has been modified to include vascularized bone marrow in intrinsically chimeric 11 SIEA myocutaneous/vascularized femur transplants. 12,13 However, in previous experiments we noted autocannibalization of orthotopically inset SIEA flaps with subsequent infection in allorecipients maintained on experimental immunosuppression, complicating clinical and histologic evaluation of rejection.…”

Immunologic Approaches to Composite Tissue Allograft

“…Although the reason for the lack of GVHD in this model is still undetermined, the authors hypothesize that the stromal microenvironment may be responsible because of its multiple sources of signaling mechanisms. 81 …”