Background and Objective

Vascularized composite allotransplantation suffer chronic rejection modulated by cytokines. Reverse chimerism or allograft chimerism is defined as the repopulation of the transplanted tissue by circulating cells of the recipient. Plerixafor mobilizes CD34+ bone marrow stem cells to the peripheral blood.

The aim of the study was to know the molecular mechanisms involved in chronic rejection and reverse chimerism after plerixafor administration.

Methods

Sixteen heterotopic osteomuscular hindlimb transplants were performed between female Brown-Norway rats as donors and male Wistar Lewis rats as recipients under subtherapeutic immunosuppression with tacrolimus. Two groups were established according to the postoperative administration of plerixafor. After 9 weeks, expression of cytokines and leukocyte infiltration were studied in different muscle locations, as well as the degree of chronic rejection and percentage of reverse chimerism in different tissues of the allograft.

Results

Statistical differences were found in granulocyte colony stimulating factor and interleukin 12 expression at middle and distal allograft thirds, and interleukin 6 expression at middle allograft third. The intensity of leukocyte infiltration was greater in the group that did not receive plerixafor. Both groups developed chronic rejection and the appearance of reverse chimerism could be observed. However, no significant differences were observed in leukocyte infiltration, chronic rejection or reverse chimerism.

Conclusions

The mobilization of CD34+ bone marrow stem cells was associated with a lower expression of granulocytic colony stimulating factor, interleukin 6 and interleukin 12.

These findings contribute to elucidate the molecular mechanisms that could lead to the creation of chimeras in the allograft.

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