Cell traffic between donor and recipient following rat limb allograft

Abstract

Although cell traffic from the graft into the recipient and from the recipient into the graft had been noticed in allogeneic organ transplantation, little is known following whole-limb allografting. This study was conducted to define cell migration between donor and recipient. Sixty-seven vascularized hind limb allotransplantations were performed in rat sex-mismatched pairs and the recipient animals were treated with FK506 immunosuppression. The ratio of donor and recipient cells was evaluated by semi-quantitative PCR using the specific primers of the Y-chromosome. Allografted limbs had no rejection episode until the final assessment. The male recipient cells were detected in female limb grafts not at 1 week but at 48 weeks after transplantation. The male donor cells were detected in the humerus and tibia in the female recipient but not in the gastrocnemius muscle and leg skin. Our results demonstrated that recipient-derived cells gradually migrated into the grafted bone, muscle and skin cells with the duration of time. Donor-derived cells migrated into the healthy bones but not into the healthy muscle and skin. Because active regeneration occurs in the grafted limb to compensate graft damage secondary to ischemia and operative intervention, recipient-derived cells may mediate a muscular and dermo-epidermal renewal.

Prolonged survival of experimental extremity allografts: A new protocol with total body irradiation, granulocyte-colony stimulation factor, and FK506

“…However, donor cells in the vascularized bone marrow were eventually replaced by recipient cells, and there was no long‐term increase in chimerism. Our previous study demonstrated similar results, with the level of bone marrow chimerism being 1% at 24 weeks and 10% at 48 weeks 13…”

Cell lineage in vascularized bone transplantation

“…This extend of chimerism at 18 weeks was also found by Pelzer et al, who describes 81% of bone cells in immunosuppressed allotransplants to be recipient derived at 18 weeks . Equally, Muramatsu et al determined allotransplant cell lineage in rats with semiquantitative PCR techniques and found that by 24 weeks approximately 90% of fresh allotransplant bone had been repopulated by recipient cells . Despite the dimensional differences between rat and human bone, the rate of bone remodeling has been found to be comparable between rodent and human bone .…”

“…We applied a sexmismatch rat model that has been used successfully in our previous bone transplantation research. [15][16][17] This transplantation model allows the study of cell lineage with quantitative RT-PCR on the Sry and cyclophilin housekeeper genes to detect the relative amount of recipient cells to donor cells within the transplant. Laser capture microdissection facilitates highly selective harvest of tissue, without contamination of adjacent soft tissue including capillary tissue.…”

Myeloablative Irradiation, Granulocyte-Colony Stimulating Factor, and FK506 can Induce Macrochimerism and Prolong the Survival of Experimental Extremity Allografts

“…They have proven to be an important model for elucidating the mechanism of transplantation tolerance because the bone marrow is surgically grafted with its microenvironment intact. Our previous study demonstrated migration of donororigin cells into the recipient's lymphoid tissues, however the donor/recipient cell ratio remained unexpectedly low, resulting in microchimerism [25]. There have also been clinical reports of unexpectedly low levels of chimerism after CTA [26].…”