Dumbill Richard, Laurenson-Schafer Hannah, Sharples Edward J, Barnes James, Mittal Shruti, Friend Peter J, Clark Anne
Nuffield Department of Surgical Sciences, University of Oxford, Churchill Hospital, Oxford, United Kingdom.
Diabetes Research Laboratories, Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Oxford, United Kingdom.
Transplant Direct. 2020 Oct 19;6(11):e613. doi: 10.1097/TXD.0000000000001059. eCollection 2020 Nov.
Whole pancreas transplantation (Tx) is a successful treatment for type 1 diabetes resulting in independence from antidiabetic therapies. Transplant-related factors contributing to pancreatic islet failure are largely unknown; both recurring insulitis and pancreatitis have been implicated. The aim was to determine if cellular changes in islets and exocrine tissue are evident early in Tx, which could contribute to eventual graft failure using well-preserved tissue of grafts explanted from largely normoglycemic recipients.
Histological specimens of explants (n = 31), Tx duration 1 day-8 years (median 29 d), cold ischemia time 7.2-17.3 hours (median 11.1 h), donor age 13-54 years (median 38 y) were examined; sections were labeled for inflammation, islet amyloidosis, and tissue fibrosis, and morphometry performed on immunolabeled insulin and glucagon positive islet cells. Data were related to clinical details of donor, recipient, and features of Tx.
Islet inflammation consistent with recurrent insulitis was not seen in any sample. Insulin-labeled islet cell proportion decreased with donor age ( < 0.05) and cold ischemia ( < 0.01) in explants from 26 normoglycemic patients; glucagon-labeled area proportion increased with cold ischemia ( < 0.05). Clinical pancreatitis was the explant reason in 12 of 28 normoglycemic cases. Exocrine fibrotic area/pancreas was variable (0.7%-55%) and unrelated to clinical/pathological features. Islet amyloid was present in 3 normoglycemic cases (donor ages 58, 42, and 31 y; Tx duration 8 y, 31 and 33 d, respectively). In 1 patient receiving antidiabetic therapy, the insulin-labeled area was reduced but with no evidence of islet inflammation.
Explant histological changes after short-term Tx are similar to those seen in type 2 diabetes and occur in the absence of immunologic rejection without causing hyperglycemia. This suggests that factors associated with Tx affect islet stability; persistent deterioration of islet integrity and exocrine tissue fibrosis could impact on sustainability of islet function.
全胰腺移植是治疗1型糖尿病的一种成功方法，可使患者不再依赖抗糖尿病治疗。导致胰岛移植失败的移植相关因素在很大程度上尚不清楚；复发性胰岛炎和胰腺炎都被认为与之有关。本研究旨在确定在移植早期胰岛和外分泌组织中是否存在明显的细胞变化，这可能导致使用来自血糖基本正常的受者的保存良好的移植组织最终出现移植失败。
检查了31个移植胰腺外植体的组织学标本，移植时间为1天至8年（中位数为29天），冷缺血时间为7.2至17.3小时（中位数为11.1小时），供体年龄为13至54岁（中位数为38岁）；切片进行炎症、胰岛淀粉样变性和组织纤维化标记，并对免疫标记的胰岛素和胰高血糖素阳性胰岛细胞进行形态测量。数据与供体、受体的临床细节以及移植特征相关。
在任何样本中均未发现与复发性胰岛炎一致的胰岛炎症。来自26例血糖正常患者的移植胰腺外植体中，胰岛素标记的胰岛细胞比例随供体年龄降低（P<0.05）和冷缺血时间增加而降低（P<0.01）；胰高血糖素标记的面积比例随冷缺血时间增加而增加（P<0.05）。在28例血糖正常的病例中，有12例因临床胰腺炎而切除移植胰腺。外分泌纤维化面积/胰腺的比例各不相同（0.7%至55%），且与临床/病理特征无关。3例血糖正常的病例中存在胰岛淀粉样变（供体年龄分别为58岁、42岁和31岁；移植时间分别为8年、31天和33天）。在1例接受抗糖尿病治疗的患者中，胰岛素标记的面积减少，但没有胰岛炎症的证据。
短期移植后移植胰腺外植体的组织学变化与2型糖尿病相似，在无免疫排斥反应的情况下发生，且不导致高血糖。这表明与移植相关的因素会影响胰岛的稳定性；胰岛完整性的持续恶化和外分泌组织纤维化可能会影响胰岛功能的可持续性。
