Stegall M D
University of Colorado School of Medicine, Denver, USA.
Ann Transplant. 1997;2(3):8-11.
Despite the increasing success of whole-organ pancreas transplantation, the success of clinical islet allografts has remained limited. One of the factors limiting the success is the difficulty in monitoring islet allografts after transplantation. The aim of these studies is to develop a method of "biopsying" human islet allografts using a forearm islet implantation site.
A subtherapeutic number of isolated human islets were placed in the forearm under the muscle fascia in three human recipients with Type I insulin dependent diabetes. All of the recipients had undergone successful cadaveric renal transplantation at least one year prior and were maintained on their baseline immunosuppression. Aliquots of the islet grafts were removed 7 and 14 days to assess engraftment and graft infiltrate. To verify that the islets were viable, 400 were handpicked and transplanted into B6-scid mice made diabetic with streptozotocin.
The biopsy site was found in all three cases. In one patient, no islets were recovered. In two other patients, viable islet tissue was recovered 7 days after transplantation. Immunohistology at 7 days showed the presence of both insulin and glucagon-staining cells in the islets. At 14 days in these two patients, a mononuclear cell infiltrate was observed in the explanted islet biopsies. Immunohistology showed the relative absence of insulin-staining cells with intact glucagon-staining cells. This finding is consistent with recurrent autoimmunity in the islet grafts.
This preliminary study shows that the forearm biopsy site is a useful method to retrieve human islet grafts after transplantation. The islets engraft and are easily found in the first weeks after transplantation. These data suggest that recurrent autoimmunity may affect islet allografts. Further studies will be needed to determine if the histology in the forearm will correlate with the fate of intraportal or intraperitoneal islet allografts. Although they were shown to reduce the incidence of early allograft failure, their influence on the long-term graft survival remains to be proven.
尽管全胰腺移植的成功率不断提高，但临床胰岛同种异体移植的成功率仍然有限。限制成功的因素之一是移植后监测胰岛同种异体移植的困难。这些研究的目的是开发一种利用前臂胰岛植入部位对人胰岛同种异体移植进行“活检”的方法。
将亚治疗剂量的分离人胰岛置于三名I型胰岛素依赖型糖尿病患者前臂的肌筋膜下。所有受者至少在一年前接受了成功的尸体肾移植，并维持其基线免疫抑制状态。在第7天和第14天取出胰岛移植物的等分试样，以评估植入情况和移植物浸润情况。为了验证胰岛是否存活，挑选400个胰岛移植到用链脲佐菌素诱导糖尿病的B6-scid小鼠体内。
在所有三例中均发现了活检部位。一名患者未回收胰岛。在另外两名患者中，移植后7天回收了存活的胰岛组织。移植后7天的免疫组织学显示胰岛中存在胰岛素和胰高血糖素染色细胞。在这两名患者移植后14天，在外植的胰岛活检中观察到单核细胞浸润。免疫组织学显示胰岛素染色细胞相对缺乏，而胰高血糖素染色细胞完整。这一发现与胰岛移植物中复发性自身免疫一致。
这项初步研究表明，前臂活检部位是移植后获取人胰岛移植物的一种有用方法。胰岛在移植后的最初几周内植入并易于发现。这些数据表明复发性自身免疫可能影响胰岛同种异体移植。需要进一步研究以确定前臂的组织学是否与门静脉内或腹腔内胰岛同种异体移植的命运相关。尽管它们已被证明可降低早期移植物失败的发生率，但其对长期移植物存活的影响仍有待证实。
