The James Buchanan Brady Urological Institute and Department of Urology, The Johns Hopkins University School of Medicine, Baltimore, MD.
Department of Urology, Doai Memorial Hospital and The University of Tokyo, Tokyo, Japan.
Eur Urol. 2017 Apr;71(4):584-593. doi: 10.1016/j.eururo.2016.07.006. Epub 2016 Jul 16.
BACKGROUND: Penile transplantation is a potential treatment option for severe penile tissue loss. Models of human penile rejection are lacking. OBJECTIVE: Evaluate effects of rejection and immunosuppression on cavernous tissue using a novel ex vivo mixed lymphocyte reaction (MLR) model. DESIGN, SETTING, AND PARTICIPANTS: Cavernous tissue and peripheral blood mononuclear cells (PBMCs) from 10 patients undergoing penile prosthesis operations and PBMCs from a healthy volunteer were obtained. Ex vivo MLRs were prepared by culturing cavernous tissue for 48h in media alone, in media with autologous PBMCs, or in media with allogenic PBMCs to simulate control, autotransplant, and allogenic transplant conditions with or without 1μM cyclosporine A (CsA) or 20nM tacrolimus (FK506) treatment. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Rejection was characterized by PBMC flow cytometry and gene expression transplant array. Cavernous tissues were evaluated by histomorphology and myography to assess contraction and relaxation. Data were analyzed using two-way analysis of variance and unpaired Student t test. RESULTS AND LIMITATIONS: Flow cytometry and tissue array demonstrated allogenic PBMC activation consistent with rejection. Rejection impaired cavernous tissue physiology and was associated with cellular infiltration and apoptosis. CsA prevented rejection but did not improve tissue relaxation. CsA treatment impaired relaxation in tissues cultured without PBMCs compared with media and FK506. Study limitations included the use of penile tissue with erectile dysfunction and lack of cross-matching data. CONCLUSIONS: This model could be used to investigate the effects of penile rejection and immunosuppression. Additional studies are needed to optimize immunosuppression to prevent rejection and maximize corporal tissue physiology. PATIENT SUMMARY: This report describes a novel ex vivo model of human penile transplantation rejection. Tissue rejection impaired erectile tissue physiology. This report suggests that cyclosporin A might hinder corporal physiology and that other immunosuppressant agents, such as FK506, might be better suited to penile transplantation.
背景：阴茎移植是治疗严重阴茎组织缺失的一种潜在治疗方法。目前缺乏人类阴茎排斥反应的模型。
目的：使用新型离体混合淋巴细胞反应（MLR）模型评估排斥反应和免疫抑制对海绵体组织的影响。
设计、设置和参与者：从 10 名接受阴茎假体手术的患者中获取海绵体组织和外周血单核细胞（PBMC），并从健康志愿者中获取 PBMC。通过将海绵体组织在培养基中单独培养 48 小时、在含有自体 PBMC 的培养基中或在含有同种异体 PBMC 的培养基中培养，制备离体 MLR，以模拟对照、自体移植和同种异体移植条件，并在有或没有 1μM 环孢素 A（CsA）或 20nM 他克莫司（FK506）治疗的情况下进行培养。
观察指标和统计学分析：通过 PBMC 流式细胞术和基因表达移植数组来描述排斥反应。通过组织形态学和肌描记术评估海绵体组织以评估收缩和松弛。使用双向方差分析和未配对学生 t 检验分析数据。
结果和局限性：流式细胞术和组织数组显示同种异体 PBMC 激活与排斥反应一致。排斥反应损害了海绵体组织生理学，并与细胞浸润和细胞凋亡有关。CsA 可预防排斥反应，但不能改善组织松弛。与培养基和 FK506 相比，CsA 处理会损害未培养 PBMC 的组织松弛。研究局限性包括使用患有勃起功能障碍的阴茎组织和缺乏交叉匹配数据。
结论：该模型可用于研究阴茎排斥反应和免疫抑制的影响。需要进一步研究来优化免疫抑制以预防排斥反应并最大限度地提高 corporal 组织生理学。
患者总结：本报告描述了一种新型的人类阴茎移植排斥反应离体模型。组织排斥反应损害了勃起组织生理学。本报告表明环孢素 A 可能会阻碍 corporal 生理学，而其他免疫抑制剂，如 FK506，可能更适合阴茎移植。
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