Department of Chemical and Biotechnological Engineering, Université de Sherbrooke, 2500, boulevard de l'Université, J1K 2R1 Sherbrooke, Québec, Canada.
PhenoSwitch Bioscience, Faculty of Medicine and Health Sciences, Université de Sherbrooke, J1H 5N4 Sherbrooke, Québec, Canada.
Curr Res Transl Med. 2017 Jan-Mar;65(1):31-39. doi: 10.1016/j.retram.2016.10.001. Epub 2016 Nov 7.
The epidemic expansion of diabetes is a major concern of public health. A promising treatment is the transplantation of islets of Langerhans isolated from the whole pancreas but the yields of islets isolation and the rates of successful engraftments still have to be improved to make this therapy effective. The extracellular matrix (ECM) of the pancreatic tissue is partially lost during the isolation process and a comprehensive knowledge of the pancreatic ECM composition and organization could identify targets to improve islets isolation and transplantation or highlight new therapeutics for pancreatic diseases. The organization, composition and three-dimensional architecture of the pancreatic ECM were analysed in mouse and pig by three different techniques. Laminin α-4 and β-2 chains are localized by immunohistochemistry in the exocrine tissue and inside islets of mouse pancreas but not around islets that are surrounded by an ECM made of collagen type IV and type V. Collagen type I, III, and VI were identified by proteomics as specific constituents of the pig pancreatic ECM along with the low-abundance isoforms α3(IV) α4(IV) α5(IV) and α1(V) α2(V) α3(V) of collagen type IV and type V respectively. The three-dimensional ECM architecture is analysed on decellularized mouse pancreas by scanning electron microscopy and is organized in honeycomb structures made of thin ECM fibers assembled in thicker bundles. The combination of immunohistochemistry, proteomics and scanning electron microscopy gives complementary perspective on the pancreatic ECM composition and organization. It represents a valuable toolbox for deeper investigations of ECMs and proposes clues in tissue engineering of the pancreas.
糖尿病的流行是公共卫生的主要关注点之一。有前途的治疗方法是移植从整个胰腺中分离出来的胰岛，但胰岛的分离产量和成功移植的比例仍有待提高，以使这种治疗方法有效。在分离过程中，胰腺组织的细胞外基质（ECM）部分丢失，如果全面了解胰腺 ECM 的组成和组织，就可以确定改善胰岛分离和移植的目标，或突出用于治疗胰腺疾病的新疗法。通过三种不同的技术分析了小鼠和猪胰腺的 ECM 组织、组成和三维结构。免疫组织化学定位显示，在小鼠胰腺的外分泌组织和胰岛内部存在层粘连蛋白α-4 和 β-2 链，但在胰岛周围没有发现，胰岛周围的 ECM 由Ⅳ型和Ⅴ型胶原组成。蛋白质组学鉴定出胶原Ⅰ、Ⅲ和Ⅵ是猪胰腺 ECM 的特定成分，同时还鉴定出了Ⅳ型和Ⅴ型胶原的低丰度同工型α3(IV)、α4(IV)、α5(IV)和α1(V)、α2(V)、α3(V)。通过扫描电子显微镜对脱细胞化的小鼠胰腺进行了三维 ECM 结构分析，发现 ECM 纤维组装在较厚的束中，形成了蜂窝状结构。免疫组织化学、蛋白质组学和扫描电子显微镜的结合为胰腺 ECM 的组成和组织提供了互补的视角。它为 ECM 的深入研究提供了一个有价值的工具箱，并为胰腺组织工程提出了线索。
