A new total hemiface allotransplantation model in rats

Külahçi, Yalçın; Altuntaş, Selman Hakkı; Karagöz, Hüseyi̇n; Cwykiel, Joanna; Zor, Fatih; Siemionow, Maria

doi:10.1002/micr.22527

Cited by 9 publications

(4 citation statements)

References 33 publications

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“…The xenografts were evaluated on a daily basis for any signs of flap failure and rejection as described in the literature (Casal et al, 2017; Kulahci et al, 2016; Ozmen et al, 2006; Zor et al, 2019). In the early postoperative period, skin flap was monitored clinically by color, warmth, and refill.…”

Section: Methodsmentioning

confidence: 99%

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Composite tissue xenopreservation: Preliminary results of staged VCA in rat to mouse model

et al. 2023

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BackgroundThe time between procurement and transplantation of composite tissues, especially regarding the limited donor pool, is a challenge effecting the outcomes of the transplantation. Current preservation techniques mainly include either cold preservation with a solution or machine perfusion using blood or certain oxygen‐carrying solutions. However, none enables preservation beyond 24 h. Increasing this time to several days will provide better usage of the donor pool, safer transplantation of VCA with significant muscle content, and gives time to stabilize a patient before long surgical procedures. Herein, we described a novel strategy of xenopreservation (preservation via xenotransplantation) to preserve composite tissues for 7 days, followed by staged transplantation.Materials and MethodsWe used two concordant species, female Sprague Dawley rats (n = 10) and female CF‐1 mice (n = 10) in this study. Four of pair of animals are used for anatomical study. The groin flap of the rat was used as a xenograft and xenotransplanted to the neck area of the carrier mouse. Cyclosporine (CsA) was administered used as immunosuppressant. After 7 days of preservation on the mouse neck, xenotransplanted groin flap (called xenopreserved flap) was re‐harvested, skin and vessels samples were collected for histopathological evaluation, and the xenopreserved flap was transplanted to the donor rat's opposite groin area. Anastomoses were performed between the flap's pedicle and the femoral vessels. Clinical observation regarding inflammation and tissue perfusion of the xenopreserved flap was monitored daily. Fifteen days after the second surgical procedure, the rats were euthanized, and skin and vessel samples were collected. Histologic evaluation, including inflammatory cell numbers, was performed. Wilcoxon test was used to compare the changes in inflammation severity and p < .05 was set for statistical significance.ResultsAll xenopreserved groin flaps except one survived. Mean lymphocyte count before the second operation (at the end of the xenopreservation procedure) was 20,22 ± 0.44 and reduced to 13,14 ± 0.47 at the end of 15 days, and the difference was statistically significant (p < .05).ConclusionThis proof‐of‐concept study with preliminary results showed that xenotransplantation might be a novel strategy for preservation of VCA for a certain period of time. However, additional translational studies are needed to modulate the tissue changes following xenopreservation.

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Section: Methodsmentioning

confidence: 99%

“…The xenografts were evaluated on a daily basis for any signs of flap failure and rejection as described in the literature (Casal et al, 2017;Kulahci et al, 2016;Ozmen et al, 2006;Zor et al, 2019). decided by for hair loss, desquamation, epidermolysis, exudation, and stiffness.…”

Section: First Operationmentioning

confidence: 99%

Composite tissue xenopreservation: Preliminary results of staged VCA in rat to mouse model

et al. 2023

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“…Transplantation of a whisker-containing rat mystacial pad is a versatile VCA model ( 11 – 14 ). However, the lack of its bony component resulted in the need for long-term immunosuppression.…”

Section: Introductionmentioning

confidence: 99%

“…A regimen with a low dose of Cyclosporine (CsA) (2 mg/kg/day) is commonly required for the entire follow-up period (200–330 days) to maintain the survival of the (modified) full face/scalp allografts from Lewis-Brown Norway (LBN) (RT11 + n) donors onto Lewis (LEW) (RT11) recipients ( 15 ). In previous studies, osseous-containing hemiface allotransplantation allowed a tapered dose of immunosuppressant while maintaining graft survival ( 13 , 14 ).…”

Section: Introductionmentioning

confidence: 99%

The intragraft vascularized bone marrow induces secondary donor-specific mystacial pad allograft tolerance

et al. 2022

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IntroductionVascularized bone marrow (VBM) is essential in tolerance induction through chimerism. We hypothesized that the inclusion of VBM contributes to the induction of mystacial pad allotransplantation tolerance.MethodIn this study, 19 VBM, nine mystacial pad, and six sequential VBM and mystacial pad allografts were transplanted from Brown Norway (BN) rats to Lewis (LEW) rats to test our hypothesis. The VBM recipients were divided into antilymphocyte serum (ALS) monotherapy group (two doses of ALS on day 3 pretransplantation and day 1 posttransplantation), immunosuppressant group [a week of 2 mg/kg/day tacrolimus (Tac) and 3 weeks of 3 mg/kg/day rapamycin (RPM)], and combined therapy group. The mystacial pad recipients were divided into VBM and non-VBM transplantation groups, and both groups were treated with an immunosuppression regimen that consists of ALS, Tac, and RPM. For the recipients of sequential VBM and mystacial pad allotransplantations, additional Tac was given 1 week after mystacial pad transplantation. Allograft survival, donor-specific tolerance, and chimerism level were evaluated.ResultsWith the administration of ALS and short-term Tac and RPM treatments, VBM recipients demonstrated long-term graft survival (>120 days) with persistent chimerism for 30 days. CD3+ T cells from tolerant rats showed donor-specific hyporesponsiveness and tolerance to donor skin grafts but not to third-party counterparts. Furthermore, mystacial pad graft recipients with VBM transplantation exhibited a higher allograft survival rate than those without VBM transplantation [median survival time (MST) >90 days vs. 70 days, p < 0.05].ConclusionThis study demonstrated that VBM transplantation is an efficient strategy to induce and maintain donor-specific tolerance for an osseous-free allograft.

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The effect of thymus transplantation on donor‐specific chimerism in the rat model of composite osseomusculocutaneous sternum, ribs, thymus, pectoralis muscles, and skin allotransplantation

et al. 2020

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IntroductionResearch on tolerance has proven that development of donor‐specific chimerism (DSC) may accompany tolerance induction in vascularized composite allotransplantation (VCA). In this study, we aimed to determine the effect of thymus transplantation on the induction of DSC in rat VCA model of osseomusculocutaneous sternum (OMCS) and osseomusculocutaneous sternum and thymus (OMCST) allotransplantation.Materials and MethodsA total of 20 Lewis‐Brown Norway and Lewis rats, 5–6 weeks old, weighting between 120 and 150 g, were used in the study. OMCS (n = 5) and OMCST (n = 5) allografts were harvested from Lewis‐Brown Norway donors (RT1l + n) based on the common carotid artery and external jugular vein, and a heterotopic transplantation was performed to the inguinal region of the Lewis (RT1l) recipients under cyclosporine A monotherapy (16 mg/kg) protocol tapered to 2 mg/kg and maintained for the duration of the study. The peripheral blood chimerism levels (T‐cell, B‐cell, and monocyte/granulocyte/dendritic cell–MGDC populations) were evaluated at days 7, 14, 35, 63, 100, and 150 posttransplant by flow cytometry. At Day 150, thymus, spleen, and liver samples were assessed by polymerase chain reaction (PCR) in the presence of DSC.ResultsTotal chimerism level increased in both OMCST and OMCS groups at all time points. At 150 days posttransplant, chimerism in OMCST group was significantly higher (12.91 ± 0.16%) than that in OMCS group (8.89 ± 0.53%%, p < .01), and PCR confirmed the presence of donor‐derived cells in the liver and spleen of all OMCST recipients and in one liver sample and two spleen samples in OMCS recipients without thymus transplant.ConclusionsThis study confirmed the direct effects of thymus transplantation on the induction and maintenance of DSC in T‐cell, B‐cell, and MGDC populations. These results confirm correlation between thymus transplantation and DSC induction.

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A new total hemiface allotransplantation model in rats

Abstract: The feasibility and long-term survival of the new hemiface VCA transplantation model was confirmed, donor-specific chimerism and post-transplant tissue changes were evaluated.

Cited by 9 publications

References 33 publications

Composite tissue xenopreservation: Preliminary results of staged VCA in rat to mouse model

Composite tissue xenopreservation: Preliminary results of staged VCA in rat to mouse model

The intragraft vascularized bone marrow induces secondary donor-specific mystacial pad allograft tolerance

The effect of thymus transplantation on donor‐specific chimerism in the rat model of composite osseomusculocutaneous sternum, ribs, thymus, pectoralis muscles, and skin allotransplantation

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