A new composite facial and scalp transplantation model in rats

There are limited sources of autogenous tissue available for reconstruction of severe facial and scalp deformities caused by extensive tumor ablation, burns, or trauma. Allografts from cadaveric sources may serve as a reconstructive alternative. However, technical and immunological aspects of harvesting and transplanting face and scalp flaps limit the routine use of such procedures. For evaluation of the feasibility of composite-tissue reconstruction, an experimental model of composite face/scalp flap transplantation in rats was designed. Technical aspects of the model, survival rates, and the complications encountered during development of the model are presented. A total of 64 animals, in three experimental groups, were studied. In group I, the anatomical study group (n = 6), the anatomical features of the face and scalp region in rats were explored. Groups II and III were the transplantation groups. Isograft transplantations were performed between identical Lewis rats (RT11 to RT11), and allografts were transplanted, across major histocompatibility complex barriers, between Lewis-Brown Norway rats (RT1l/n) and Lewis rats (RT11). In group II (the control group, n = 8), transplantation of nonvascularized composite face/scalp isografts and allografts was performed. In group III (the transplantation group, n = 50), vascularized face/scalp isografts (n = 36) and allografts (n = 14) were transplanted. Complications included partial or total flap necrosis, death attributable to food aspiration, and poor general condition. To prevent acute and chronic allograft rejection, cyclosporine A (16 mg/kg per day) therapy was initiated 24 hours after transplantation; the dose was tapered to 2 mg/kg per day within 4 weeks and was maintained at that level thereafter. Long-term survival (>170 days) was achieved, without any signs of rejection, with low-dose (2 mg/kg per day) cyclosporine A therapy. This is the first report documenting successful composite face/scalp flap transplantation in the rat model.     

Tolerance induction in composite facial allograft transplantation in the rat model

Clinical application of composite tissue allograft transplants opened discussion on the restoration of facial deformities by allotransplantation. The authors introduce a hemifacial allograft transplant model to investigate the rationale for the development of functional tolerance across the major histocompatibility complex barrier. Eighteen rats in three groups were studied. The composite hemifacial allotransplantations including the ear and scalp were performed between Lewis-Brown Norway (RT1l+n) and Lewis (RT1l) rats and isotransplantations were performed between Lewis rats. Isograft controls (n = 6) and allograft controls (n = 6) did not receive treatment. Allografts in treatment group (n = 6) were treated with cyclosporine A 16 mg/kg/day during the first week; this dose was tapered to 2 mg/kg/day over 4 weeks and maintained at this level thereafter. Functional tolerance to face allografts was evaluated clinically and histologically. Donor-specific chimerism was assessed at days 21 and 63 by flow cytometry. In vitro evaluation of donor-specific tolerance was performed by mixed lymphocyte reaction at day 160 after transplantation. Isograft controls survived indefinitely. All nontreated allografts were rejected within 5 to 7 days after transplantation, as confirmed by histopathologic analysis. Five of six face allografts under the cyclosporine A protocol showed no signs of rejection for up to 240 days and remained alive and under evaluation, whereas one animal showed signs of rejection at day 140. This was reversed by adjustment of the cyclosporine A dose. At day 21 after transplantation, flow cytometric analysis of the donor-specific chimerism showed 1.11 percent of double-positive CD4FITC/RT1Ac-Cy7 and 1.43 percent of double-positive CD8PE/RT1Ac-Cy7 T-cell populations in the peripheral blood of hemiface allotransplant recipients. The chimerism level of double-positive CD4FITC/RT1Ac-Cy7 T cells increased to 3.39 percent, whereas it remained stable for the double-positive CD8PE/RT1Ac-Cy7 T-cell population at day 63 after transplantation (1.00 percent). The mixed lymphocyte reaction assay at day 160 after transplantation revealed donor-specific tolerance to donor (Lewis-Brown Norway) antigens and strong reactivity to the third-party (ACI) alloantigens. In this study, donor-specific chimerism and functional tolerance were induced in hemifacial allograft transplants across the major histocompatibility complex barrier under cyclosporine A monotherapy protocol. This model will allow further studies on tolerance induction protocols.     

Dynamic reconstruction of eye closure by muscle transposition or functional muscle transplantation in facial palsy

For patients with facial palsy, lagophthalmus is often a more serious problem than the inability to smile. Dynamic reconstruction of eye closure by muscle transposition or by free functional muscle transplantation offers a good solution for regaining near-normal eye protection without the need for implants. This is the first quantitative study of three-dimensional preoperative and postoperative lid movements in patients treated for facial paralysis. Between February of 1998 and April of 2002, 44 patients were treated for facial palsy, including reconstruction of eye closure. Temporalis muscle transposition to the eye was used in 34 cases, and a regionally differentiated part of a free gracilis muscle transplant after double cross-face nerve grafting was used in 10 cases. Patients' facial movements were documented by a three-dimensional video analysis system preoperatively and 6, 12, 18, and 24 months postoperatively. For this comparative study, only the data of patients with preoperative and 12-month postoperative measurements were included. In the 27 patients with a final result after temporalis muscle transposition for eye closure, the distance between the upper and lower eyelid points during eye closing (as for sleep) was reduced from 10.33 +/- 2.43 mm (mean +/- SD) preoperatively to 5.84 +/- 4.34 mm postoperatively on the paralyzed side, compared with 0.0 +/- 0.0 mm preoperatively and postoperatively on the contralateral healthy side. In the resting position, preoperative values for the paralyzed side changed from 15.11 +/- 1.92 mm preoperatively to 13.46 +/- 1.94 mm postoperatively, compared with 12.17 +/- 2.02 mm preoperatively and 12.05 +/- 1.95 mm postoperatively on the healthy side. In the nine patients with a final result after surgery using a part of the free gracilis muscle transplant reinnervated by a zygomatic branch of the contralateral healthy side through a cross-face nerve graft, eyelid closure changed from 10.21 +/- 2.72 mm to 1.68 +/- 1.35 mm, compared with 13.70 +/- 1.56 mm to 6.63 +/- 1.51 mm preoperatively. The average closure for the healthy side was from 11.20 +/- 3.11 mm to 0.0 +/- 0.0 mm preoperatively and from 12.70 +/- 1.95 mm to 0.0 +/- 0.0 mm postoperatively. In three cases, the resting tonus of the part of the gracilis muscle transplant around the eye had increased to an extent that muscle weakening became necessary. Temporalis muscle transposition and free functional muscle transplantation for reanimation of the eye and mouth at the same time are reliable methods for reconstructing eye closure, with clinically adequate results. Detailed analysis of the resulting facial movements led to an important improvement of the authors' operative techniques within the last few years. Thus, the number of secondary operative corrections could be significantly reduced. These qualitative and quantitative studies of the reconstructed lid movements by three-dimensional video analysis support the authors' clinical concept of temporalis muscle transposition being the first-choice method in adult patients with facial palsy. In children, free muscle transplantation is preferred for eye closure, so as not to interfere with the growth of the face by transposition of a masticatory muscle. In addition, a higher degree of central plasticity in children might be expected.     

Dendritic cells transfected with PD-L1 recombinant adenovirus induces T cell suppression and long-term acceptance of allograft transplantation

The purpose of this study is to assess the potential of dendritic cells transfected with PD-L1 recombinant adenovirus induces CD8+ T cell suppression and kidney allograft tolerance. To prove it, DCs transfected with PD-L1 recombinant adenovirus (DC/Ad-PD-L1) were transferred into the MHC-mismatched rat kidney transplants. After kidney transplantation, the mixed lymphocyte reaction (MLR) assay and kidney function were analyzed. The results demonstrated that after administration of DC/Ad-PD-L1, the proliferation, cytokines secretion and activation marker expression of CD8+ T cells were suppressed. In addition, DC/Ad-PD-L1 could improve kidney function and survival of transplants. The findings suggested that DC/Ad-PD-L1 could induce CD8+ T cell tolerance and lead to kidney allograft tolerance, which provided a promising finding for clinical application.     

Thromboembolic risk factors in kidney transplantation: hemorheologic examination in secondary polycythemia

Cardiovascular risk factors will increase the lethality of kidney patients being under dialysis treatment and after transplantation. This risk is additionally increased after transplantation by secondary polycythemia. The paper investigates the rheological properties of the blood of 20 patients affected by secondary polycythemia after kidney transplantation, 10 patients without polycythemia after kidney transplantation and 19 test persons. Plasma viscosity, erythrocyte aggregation and whole blood viscosity were determined. As a result, an increase of erythrocyte aggregation without their deformability being changed could be found in patients affected by polycythemia after kidney transplantation. The reduced thrombocyte aggregation identified in these patients can be explained by the influence of therapy.