A Mouse Model of Vascularized Skin Transplantation

A Mouse Model of Vascularized Skin Transplantation
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DOI:
10.1097/sap.0000000000000966
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发表时间:
2017-05-01
影响因子:
1.5
通讯作者:
Guo, Shuzhong
Guo, Shuzhong
中科院分区:
医学4区
文献类型:
--
作者:
Ding, Jianke;Su, Yingjun;Guo, Shuzhong

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背景:同种异体皮肤组织抗原性强,复合组织移植后可诱导强烈的免疫排斥反应。小鼠模型在免疫排斥的机制研究中具有优势。然而,由于缝合技术在血管吻合方面的技术挑战,小鼠带血管的同种异体皮肤移植模型在免疫排斥研究中的应用并不广泛。方法:将BALB/c或C57BL/6小鼠的腹股沟游离皮瓣移植到C57BL/6小鼠的腹股沟或颈部。采用非缝合袖套技术将供体血管与IVST受者的股血管或CVST小鼠的颈总动脉和颈外静脉吻合。结果:CVST的总成功率(88.5%)高于IVST(78.9%)。CVST小鼠的总手术时间为96分钟(95%可信区间,92-101分钟),短于IVST小鼠(136分钟,95%可信区间,127-176分钟;P<0.01)。IVST小鼠出现后肢坏死和自残等并发症。雷帕霉素(3 mg/kg,每日)显著延长带血管同种异体皮肤移植的存活时间,中位存活时间为80天。结论:我们建立了一种新的小鼠带血管皮肤移植模型,该模型可用于临床相关皮肤排斥和耐受的研究。
Background: Allogeneic skin tissues are highly antigenic and induce intensive immune rejection after composite tissue allotransplantation. Mouse models have advantages in mechanistic studies of immune rejection. However, due to technical challenge in vascular anastomosis with suture technique, mouse vascularized skin allotransplantation models are not widely used in studies of immune rejection. Therefore, the authors propose vascular anastomosis through cuff technique during allotransplantation of mouse donor free groin skin flaps to either recipient inguinal or cervical site.Methods: Free groin skin flaps from BALB/c or C57BL/6 donor mice were transplanted to the groin (inguinal vascularized skin transplantation [IVST]) or to the neck of recipient sites (cervical vascularized skin transplantation [CVST]) of C57BL/6 mice. A nonsuture cuff technique was utilized to anastomose the donor vessels with either femoral vessels in IVST recipients or common carotid arteries and external jugular veins in CVST mice. Immunosuppressant drugs were used in the allogeneic skin group.Results: The overall success rate was higher in the CVST (88.5%) when compared with the IVST (78.9%). Total operation time in CVST mice lasted 96 minutes (95% confidence interval, 92-101 minutes) that was shorter than that for IVST mice (136 minutes, 95% confidence interval, 127-176 minutes; P < 0.01). Complications, such as hindlimb necrosis and self-mutilation, were observed in IVST mice. Rapamycin (3 mg/kg, daily) significantly prolonged vascularized skin allografts survival with median survival time of 80 days. All syngeneic grafts survived for more than 80 days.Conclusions: We developed a novel mouse vascularized skin transplantation model that is feasible for the study of clinically relevant skin rejection and tolerance.