Rat model of heterotopic toe allotransplantation

Finger allotransplantation is a promising treatment for severe finger destruction. However, more research is required to decrease the risks of this procedure to a level at which the clinical use of this non-life-saving procedure is justified. A proper animal model is essential for the required experiments.

In this article, we established a toe transplantation model based on anatomic studies. A tapered dose of Cyclosporine A (CsA) was used as an immunosuppressive therapy in the Brown Norway-to-Lewis allotransplantation experimental group, whereas isotransplantation or allotransplantation without treatment or with ligated pedicles was performed on the control groups. Recipients were assessed daily after operation for any signs of rejection and complications. On postoperative day 90, skin graft test was used to test the level of donor-specific tolerance in the recipients. On postoperative day 120, x-rays and micro-computed tomographies were performed for bone morphology evaluation. The chimerism in the recipient peripheral blood, lymph node, spleen, and thymus was tested by flow cytometry and immunohistochemical staining. And histologic study of the toe grafts and skin grafts were carried out.

The blood supply of the toe graft was confirmed, and accordingly, transplantations were performed. The isografts survived indefinitely. The allografts with ligated pedicles experienced necrosis within 5 d. The allografts without treatment exhibited necrosis within 14 d. Forty percent, 20%, and 40% of the allografts associated with the CsA treatment experienced severe rejection, mild rejection, and nonrejection, according to gross graft appearance, respectively. Skin grafting tests showed three different types of results. X-rays and micro-computed tomographies reveal nearly normal bone morphologies in the bone structures of all surviving animals with grafts. Low levels of donor-specific chimerism were detected in the peripheral blood samples. Spleen, lymph node, and thymus chimerism were also confirmed in the long-term surviving animals with allografts. Histologic evaluation of the long-term survivals revealed similar graft morphologies in the isografts and the nonrejected allografts, inflammatory cell infiltration in the mildly rejected allografts, and degraded cutaneous appendages in the severely rejected allografts.

We established a toe allotransplantation model. Moreover, the low rate of chimerism did not introduce specific tolerance, which might explain the high rejection rate. This model might facilitate future research in finger allotransplantation.