Bray Peter W, Neligan Peter C, Bowen C Vaughan A, Boyer Martin I
Division of Surgical Research, The Hospital for Sick Children, 555 University Avenue, Toronto, ON M5G 1X8, Canada.
J Bone Joint Surg Am. 2004 Feb;86(2):281-9. doi: 10.2106/00004623-200402000-00010.
Physeal necrosis following vascularized allograft transplantation occurs because of vascular rejection. The effect of immunosuppression withdrawal on physeal viability after bone-healing to the recipient site was investigated with use of a validated model for heterotopic microvascular transplantation of rabbit tibial physeal allografts. Our hypothesis was that an allograft survives after withdrawal of immunosuppression only if bone-healing, and therefore epiphyseal and metaphyseal vascular continuity, occurs between the transplanted physis and the recipient bone.
Physeal grafts with adjacent exposed epiphyseal and metaphyseal bone were transplanted to allogeneic recipients. Graft circulation was restored microsurgically. The immunosuppression regimen consisted of cyclosporine, administered for six weeks, followed by withdrawal of immunosuppression for four weeks. The animals were killed at ten weeks postoperatively. Group I consisted of twelve allografts that were transferred with bone contact between the transplanted graft and the iliac crest recipient site, whereas group II consisted of twelve allografts transplanted without bone contact. Control groups had identical surgical procedures without immunosuppression. Longitudinal growth was assessed by fine-detail radiography, and osseous union was evaluated histologically. Transplanted physes were evaluated histologically, and cellular viability was quantified by bromodeoxyuridine uptake. Two-way analysis of variance was used to compare physeal viability between groups.
Following immunosuppression withdrawal, the physeal grafts with bone contact had significantly greater viability indices (16.0 +/- 2.9 compared with 0.0 +/- 0.0, p < 0.005) and decreased longitudinal growth (5.1 +/- 1.9 mm compared with 10.3 +/- 3.5 mm, p < 0.05), and they demonstrated histological features that were consistent with continued viability associated with mild rejection compared with grafts transplanted without bone contact. Abnormalities of physeal architecture, however, were seen routinely. All control physes transferred without immunosuppression were nonviable and did not grow.
The viability of physeal allograft transplants is preserved following the withdrawal of immunosuppression, provided that the graft design and recipient site preparation allow for epiphyseal and metaphyseal neovascularization mediated by bone-healing between graft and recipient.
带血管异体移植后发生的骺板坏死是由血管排斥反应所致。我们使用经过验证的兔胫骨骺板异体移植物异位微血管移植模型,研究了免疫抑制撤除对骨愈合至受体部位后骺板活力的影响。我们的假设是,只有当移植的骺板与受体骨之间发生骨愈合,进而实现骨骺和干骺端血管连续性时,免疫抑制撤除后异体移植物才能存活。
将带有相邻暴露骨骺和干骺端骨的骺板移植物移植到同种异体受体。通过显微外科手术恢复移植物血液循环。免疫抑制方案包括给予环孢素六周,随后撤除免疫抑制四周。术后十周处死动物。第一组由十二个异体移植物组成,这些移植物在移植的移植物与髂嵴受体部位之间有骨接触;而第二组由十二个无骨接触移植的异体移植物组成。对照组进行相同的手术操作但不进行免疫抑制。通过详细的X线摄影评估纵向生长,并通过组织学评估骨愈合情况。对移植的骺板进行组织学评估,并通过溴脱氧尿苷摄取定量细胞活力。使用双向方差分析比较各组之间的骺板活力。
免疫抑制撤除后,有骨接触的骺板移植物具有显著更高的活力指数(分别为16.0±2.9和0.0±0.0,p<0.005),纵向生长减少(分别为5.1±1.9毫米和10.3±3.5毫米,p<0.05),与无骨接触移植的移植物相比,它们表现出与轻度排斥相关的持续活力一致的组织学特征。然而,骺板结构异常是常见的。所有未进行免疫抑制移植的对照骺板均无活力且不生长。
如果移植物设计和受体部位准备允许通过移植物与受体之间的骨愈合介导骨骺和干骺端新生血管形成,那么免疫抑制撤除后骺板异体移植的活力得以保留。