The Effect of Narrow-Band Ultraviolet B Irradiation on the Vascularized Composite Allotransplantation Rat Model.

INTRODUCTION: Vascularized composite allotransplantation (VCA) allows functional and esthetic reconstruction for patients with complex anatomical defects. However, acute and chronic graft rejections are significant obstacles to VCA. Ultraviolet light is an oncogenic environmental hazard. However, ultraviolet B (UVB) has an immunomodulation effect. Therefore, this study aims to elucidate the impact of UVB irradiation on the VCA rat model. METHODS: The rat vascularized bone marrow allotransplantation model was used. A vascularized bone marrow from a Brown Norway rat (RT1Ac) was transplanted into a Lewis rat (RT1Ab). The allograft and surrounding abdominal skin were exposed to narrow-band ultraviolet B (NB-UVB) (311 nm) radiation with an energy of 1350 mJ/cm2 3 times a week until the end of the study period. There were 5 study groups: syngeneic transplantation (group 1), allogeneic transplantation (group 2), allogenic transplantation-NB-UVB (group 3), allogenic transplantation-antilymphocyte serum (ALS)-tacrolimus (group 4), and allogenic transplantation-antilymphocyte serum-tacrolimus-NB-UVB (group 5). RESULTS: Group 5 had decreased graft survival compared with group 4. In the donor cell chimerism analysis, donor cell chimerism decreased significantly after UVB irradiation and was unresponsive to the administered immunosuppressants. After UVB irradiation, the CD8 T-cell ratio was increased, and the regulatory T-cell ratio was decreased. CONCLUSIONS: The preliminary data showed that NB-UVB irradiation of the VCA rat model may decrease graft survival. However, further studies are needed to elucidate the possible mechanisms of this phenomenon.

Free tissue transfers for reconstruction of weight-bearing heel defects: Flap selection, ulceration management, and contour revisions.

BACKGROUND: Soft tissue defects in the weight-bearing heel represent a reconstructive challenge because of tissue complexity and lack of local/regional coverage. This study presents our reconstruction outcomes of different defect aetiologies, reconstruction timing, and flap selection. METHODS: Patients with weight-bearing heel defects who underwent free tissue transfer from 2003 to 2014 and with at least 6 months of follow-up were retrospectively reviewed. Flap types (fasciocutaneous vs muscle/musculocutaneous), timing of reconstruction (early vs subacute vs delayed), and defect aetiology were compared in terms of flap failure, vascular complications, and ulceration. RESULTS: Seventy-four flaps were used to reconstruct weight-bearing heel defects in 70 patients. Defect aetiology included trauma in 53 patients (75%), chronic wound in 12 patients (17%), and tumour resection in 6 patients (8%). Flap survival was 97% (72/74). There was no significant difference in flap failures between muscle and fasciocutaneous flaps. The timing of reconstruction showed no difference in flap survival. There was a significant difference in ulceration rate between the trauma and non-trauma groups (p = 0.001). Twenty-eight ulcers (39%) developed, 12 (43%) of which presented 3 years postoperatively, while only 6 cases (21%) presented within one year postoperatively. CONCLUSION: Our experience represents one of the highest survival rates reported regarding free flap weight-bearing heel reconstruction. The anterolateral thigh flap was our first choice for extensive heel defects. Ulceration incidence was directly related to trauma and tends to develop 3 years after reconstruction. Delayed reconstruction was at least as safe as early or subacute reconstruction though with less need for debulking.

The intragraft vascularized bone marrow component plays a critical role in tolerance induction after reconstructive transplantation.

The role of the vascularized bone marrow component as a continuous source of donor-derived hematopoietic stem cells that facilitate tolerance induction of vascularized composite allografts is not completely understood. In this study, vascularized composite tissue allograft transplantation outcomes between recipients receiving either conventional bone marrow transplantation (CBMT) or vascularized bone marrow (VBM) transplantation from Balb/c (H2d) to C57BL/6 (H2b) mice were compared. Either high- or low-dose CBMT (1.5 × 108 or 3 × 107 bone marrow cells, respectively) was applied. In addition, recipients were treated with costimulation blockade (1 mg anti-CD154 and 0.5 mg CTLA4Ig on postoperative days 0 and 2, respectively) and short-term rapamycin (3 mg/kg/day for the first posttransplant week and then every other day for another 3 weeks). Similar to high-dose conventional bone marrow transplantation, 5/6 animals in the vascularized bone marrow group demonstrated long-term allograft survival (>120 days). In contrast, significantly shorter median survival was noted in the low-dose CBMT group (~64 days). Consistently high chimerism levels were observed in the VBM transplantation group. Notably, low levels of circulating CD4+ and CD8+ T cells and a higher ratio of Treg to Teff cells were maintained in VBM transplantation and high-dose CBMT recipients (>30 days) but not in low-dose VBM transplant recipients. Donor-specific hyporesponsiveness was shown in tolerant recipients in vitro. Removal of the vascularized bone marrow component after secondary donor-specific skin transplantation did not affect either primary allograft or secondary skin graft survival.

Immunoregulatory effects of AFP domains on monocyte-derived dendritic cell function.

BACKGROUND: Alpha-fetoprotein (AFP) is a tumor-associated glycoprotein that functions in regulation of both ontogenic and oncogenic growth. Recent study showed that AFP can induce apoptosis or impair monocyte-derived dendritic cell (MDDC) function. However, it is still unclear which AFP domain (D-AFP) plays major role in this function. RESULTS: As expected monocytes cultured in the presence of Granulocyte Macrophage-Colony Stimulating Factor (GM-CSF) and Interleukin-4 (IL-4) developed into MDDC. Up-regulation of HLA-DR and CD11c as well as loss of CD14 molecules could be observed. Full length AFP (FL-AFP), domain 2 AFP (D2-AFP) and D3-AFP, but not D1-AFP, significantly inhibited the expression of HLA-DR high/CD11c high and CD80+/CD86 high molecules. In contrast, CD83 expression was substantially down-regulated in all samples. Expression of CD40 was significantly suppressed by FL-AFP but not by any D-AFPs. Finally, both FL-AFP and D-AFP impaired the MDDC ability to secrete IL-12 (p70). CONCLUSIONS: D2- and D3- but not D1-AFP extensively suppresses the MDDC function. All the recombinant AFP proteins impaired the ability of MDDC to secrete IL-12.