AIMS/HYPOTHESIS Islets are thought to be stably present in the adult human pancreas to maintain glucose homeostasis. However, identification of the pancreatic intraepithelial neoplasia (PanIN)-islet complex in mice and the presence of PanIN lesions in adult humans suggest that similar remodelling of islet structure and environment may occur in the human pancreas. To identify islet remodelling in a clinically related setting, we examine human donor pancreases with 3D histology to detect and characterise the human PanIN-islet complex. METHODS Cadaveric donor pancreases (26-65 years old, n = 10) were fixed and sectioned (350 μm) for tissue labelling, clearing and microscopy to detect local islet remodelling for 3D analysis of the microenvironment. The remodelled microenvironment was subsequently examined via microtome-based histology for clinical assessment. RESULTS In nine pancreases, we identified the unique peri-lobular islet aggregation associated with the PanIN lesion (16 lesion-islet complexes detected; size: 3.18 ± 1.34 mm). Important features of the lesion-islet microenvironment include: (1) formation of intra-islet ducts, (2) acinar atrophy, (3) adipocyte association, (4) inflammation (CD45+), (5) stromal accumulation (α-SMA+), (6) increase in Ki-67 proliferation index but absence of Ki-67+ alpha/beta cells and (7) in-depth and continuous duct-islet cell contacts, forming a cluster. The duct-islet cell cluster and intra-islet ducts suggest likely islet cell neogenesis but not replication. CONCLUSIONS/INTERPRETATION We identify local islet remodelling associated with PanIN-islet complex in the adult human pancreas. The tissue remodelling and the evidence of inflammation and stromal accumulation suggest that the PanIN-islet complex is derived from tissue repair after a local injury.

中文翻译：

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与成人胰腺导管病变-胰岛复合体相关的局部胰岛重塑。

目的/假设 胰岛被认为稳定存在于成人胰腺中以维持葡萄糖稳态。然而，小鼠胰腺上皮内瘤变（PanIN）-胰岛复合物的鉴定以及成年人中 PanIN 病变的存在表明，人类胰腺中可能发生类似的胰岛结构和环境重塑。为了识别临床相关环境中的胰岛重塑，我们使用 3D 组织学检查人类供体胰腺，以检测和表征人类 PanIN-胰岛复合体。方法 将尸体供体胰腺（26-65 岁，n = 10）固定并切片（350 μm）进行组织标记、清除和显微镜检查，以检测局部胰岛重塑，以进行微环境的 3D 分析。随后通过基于切片机的组织学检查重塑的微环境以进行临床评估。结果 在九个胰腺中，我们确定了与 PanIN 病变相关的独特的小叶周围胰岛聚集（检测到 16 个病变-胰岛复合物；大小：3.18 ± 1.34 mm）。病变-胰岛微环境的重要特征包括：(1) 胰岛内导管的形成，(2) 腺泡萎缩，(3) 脂肪细胞结合，(4) 炎症 (CD45+)，(5) 基质积聚 (α-SMA+) , (6) Ki-67 增殖指数增加但缺乏 Ki-67+ α/β 细胞和 (7) 深入和连续的导管-胰岛细胞接触，形成一个簇。导管-胰岛细胞簇和胰岛内导管表明可能是胰岛细胞新生，但不是复制。结论/解释 我们确定了与成人胰腺中的 PanIN-胰岛复合体相关的局部胰岛重塑。组织重塑以及炎症和基质积累的证据表明，PanIN-胰岛复合物来源于局部损伤后的组织修复。