Urbanczyk Max, Abuhelou Athar, Köninger Marie, Jeyagaran Abiramy, Carvajal-Berrio Daniel, Kim Ellie, Marzi Julia, Loskill Peter, Layland Shannon L, Schenke-Layland Katja
Institute of Biomedical Engineering, Department for Medical Technologies and Regenerative Medicine, Eberhard Karls University Tübingen, Tübingen, Germany.
NMI Natural and Medical Sciences Institute at the University of Tübingen, Reutlingen, Germany, Reutlingen, Germany.
Tissue Eng Part A. 2024 Oct 25. doi: 10.1089/ten.tea.2024.0176.
Endothelial cells (ECs) play a crucial role in maintaining tissue homeostasis and functionality. Depending on their tissue of origin, ECs can be highly heterogeneous regarding their morphology, gene and protein expression, functionality, and signaling pathways. Understanding the interaction between organ-specific ECs and their surrounding tissue is therefore critical when investigating tissue homeostasis, disease development, and progression. models often lack organ-specific ECs, potentially limiting the translatability and validity of the obtained results. The goal of this study was to assess the differences between commonly used EC sources in tissue engineering applications, including human umbilical vein ECs (HUVECs), human dermal microvascular ECs (hdmvECs), and human foreskin microvascular ECs (hfmvECs), and organ-specific human pancreatic microvascular ECs (hpmvECs), and test their impact on functionality within an pancreas test system used for diabetes research. Utilizing high-resolution Raman microspectroscopy and Raman imaging in combination with established protein and gene expression analyses and exposure to defined physical signals within microfluidic cultures, we identified that ECs exhibit significant differences in their biochemical composition, relevant protein expression, angiogenic potential, and response to the application of mechanical shear stress. Proof-of-concept results showed that the coculture of isolated human islets of Langerhans with hpmvECs significantly increased the functionality when compared with control islets and islets cocultured with HUVECs. Our study demonstrates that the choice of EC type significantly impacts the experimental results, which needs to be considered when implementing ECs into models.
内皮细胞（ECs）在维持组织稳态和功能方面发挥着关键作用。根据其起源组织的不同，内皮细胞在形态、基因和蛋白质表达、功能以及信号通路方面可能具有高度异质性。因此，在研究组织稳态、疾病发展和进展时，了解器官特异性内皮细胞与其周围组织之间的相互作用至关重要。 模型通常缺乏器官特异性内皮细胞，这可能会限制所获结果的可转化性和有效性。本研究的目的是评估组织工程应用中常用的内皮细胞来源之间的差异，包括人脐静脉内皮细胞（HUVECs）、人真皮微血管内皮细胞（hdmvECs）、人包皮微血管内皮细胞（hfmvECs）以及器官特异性的人胰腺微血管内皮细胞（hpmvECs），并在用于糖尿病研究的胰腺测试系统中测试它们对功能的影响。利用高分辨率拉曼光谱和拉曼成像，结合已建立的蛋白质和基因表达分析以及在微流控培养中暴露于特定的物理信号，我们发现内皮细胞在其生化组成、相关蛋白质表达、血管生成潜力以及对机械剪切应力施加的反应方面存在显著差异。概念验证结果表明，与对照胰岛以及与HUVECs共培养的胰岛相比，分离的人胰岛与hpmvECs共培养显著提高了功能。我们的研究表明，内皮细胞类型的选择对实验结果有显著影响，在将内皮细胞应用于 模型时需要考虑这一点。
