Gotfried Y, Yaremchuk M J, Randolph M A, Weiland A J
J Bone Joint Surg Am. 1987 Mar;69(3):410-25.
Using a genetically defined rat model for the heterotopic transplantation of a vascularized knee in the rat, histological and histochemical studies of acute rejection in vascularized allografts of bone were carried out. The graft consisted of the knee joint with the distal end of the femur, the proximal part of the tibia, the cartilaginous growth plates, the articular cartilage, and a minimum cuff of muscle, which was transferred to a location under the abdominal skin. A total of 160 transplants, including vascularized and non-vascularized isografts, vascularized and non-vascularized allografts that were transplanted across a strong histocompatibility barrier, and vascularized allografts of bone that were transplanted across a weak histocompatibility barrier, were studied by light microscopy at intervals for as long as twelve weeks after transplantation. Vascularized allografts of bone that were transplanted across a strong histocompatibility barrier showed evidence of rapid rejection, similar to that after transplantation of allografts of visceral organs. This was manifested at one week by necrosis of osteocytes, cessation of microcirculatory flow, massive extravasation of red cells, and deposition of fibrin in the marrow. The large vessels demonstrated changes that were characteristic of vascular rejection. Allografts that were transplanted across a weak histocompatibility barrier showed a more gradual, less intense process of rejection that allowed observation of the evolution of the process. In these grafts, the osteoblasts and marrow in the primary spongiosa of the metaphysis were early targets of rejection, as indicated by necrosis of osteoblasts, extravasation of red blood cells, and deposition of fibrin in the marrow spaces. Loss of osteoblasts from the surfaces of osteoid as well as from bone on spicules of calcified cartilage resulted in the cessation of new-bone formation. Calcification of the longitudinal septa between the lowermost hypertrophic chondrocytes was decreased. However, the proliferation and maturation of chondrocytes in the zone of proliferating chondrocytes and in the upper hypertrophic zone continued and resulted in the formation of a thickened growth plate. The loss of osteocytes in other areas of the graft occurred later and only in the areas where the microcirculation had been lost. These data suggest that ischemic damage, which is probably secondary to an immune-related vascular compromise, is a significant factor in the failure of grafts. In the grafts that were transplanted across a weak histocompatibility barrier, the growth of new bone and revascularization by the host occurred by twelve weeks.
利用一种基因定义的大鼠模型进行大鼠带血管膝关节的异位移植，对带血管骨同种异体移植的急性排斥反应进行了组织学和组织化学研究。移植物包括膝关节以及股骨远端、胫骨近端、软骨生长板、关节软骨和最小的肌肉袖套，将其转移至腹部皮下位置。总共160例移植，包括带血管和不带血管的同基因移植、跨越强组织相容性屏障移植的带血管和不带血管的同种异体移植，以及跨越弱组织相容性屏障移植的带血管骨同种异体移植，在移植后长达12周的时间内定期通过光学显微镜进行研究。跨越强组织相容性屏障移植的带血管骨同种异体移植显示出快速排斥的迹象，类似于内脏器官同种异体移植后的情况。这在一周时表现为骨细胞坏死、微循环血流停止、红细胞大量外渗以及骨髓中纤维蛋白沉积。大血管显示出血管排斥的特征性变化。跨越弱组织相容性屏障移植的同种异体移植显示出更渐进、强度更低的排斥过程，从而能够观察到该过程的演变。在这些移植物中，干骺端初级骨小梁中的成骨细胞和骨髓是早期排斥靶点，表现为成骨细胞坏死、红细胞外渗以及骨髓腔中纤维蛋白沉积。类骨质表面和成骨针状钙化软骨上的骨表面的成骨细胞丢失导致新骨形成停止。最下层肥大软骨细胞之间纵向间隔的钙化减少。然而，增殖软骨细胞区和上层肥大区的软骨细胞增殖和成熟持续进行，并导致生长板增厚。移植物其他区域的骨细胞丢失发生较晚，且仅发生在微循环丧失的区域。这些数据表明，缺血性损伤可能继发于免疫相关的血管损害，是移植物失败的一个重要因素。在跨越弱组织相容性屏障移植并存活12周的移植物中，宿主实现了新骨生长和血管再形成。
