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用于不同内分泌起源细胞类型的高通量格式的创新多维模型。

Innovative multidimensional models in a high-throughput-format for different cell types of endocrine origin.

机构信息

Department of Endocrinology, Diabetology and Clinical Nutrition, University Hospital Zurich (USZ) and University of Zurich (UZH), Zurich, Switzerland.

Medizinische Klinik und Poliklinik III, University Hospital Carl Gustav Carus Dresden, Dresden, Germany.

出版信息

Cell Death Dis. 2022 Jul 25;13(7):648. doi: 10.1038/s41419-022-05096-x.

Abstract

The adrenal gland provides an important function by integrating neuronal, immune, vascular, metabolic and endocrine signals under a common organ capsule. It is the central organ of the stress response system and has been implicated in numerous stress-related disorders. While for other diseases, regeneration of healthy organ tissue has been aimed at such approaches are lacking for endocrine diseases - with the exception of type-I-diabetes. Moreover, adrenal tumor formation is very common, however, appropriate high-throughput applications reflecting the high heterogeneity and furthermore relevant 3D-structures in vitro are still widely lacking. Recently, we have initiated the development of standardized multidimensional models of a variety of endocrine cell/tissue sources in a new multiwell-format. Firstly, we confirmed common applicability for pancreatic pseudo-islets. Next, we translated applicability for spheroid establishment to adrenocortical cell lines as well as patient material to establish spheroids from malignant, but also benign adrenal tumors. We aimed furthermore at the development of bovine derived healthy adrenal organoids and were able to establish steroidogenic active organoids containing both, cells of cortical and medullary origin. Overall, we hope to open new avenues for basic research, endocrine cancer and adrenal tissue-replacement-therapies as we demonstrate potential for innovative mechanistic insights and personalized medicine in endocrine (tumor)-biology.

摘要

肾上腺通过在共同的器官囊内整合神经元、免疫、血管、代谢和内分泌信号,提供了一个重要的功能。它是应激反应系统的中心器官,与许多与应激相关的疾病有关。虽然对于其他疾病,已经有针对健康器官组织再生的方法,但对于内分泌疾病则缺乏这种方法——除了 1 型糖尿病。此外,肾上腺肿瘤的形成非常常见,但是,仍然缺乏合适的高通量应用,以反映体外的高度异质性和相关的 3D 结构。最近,我们已经开始在一种新的多孔板格式中开发各种内分泌细胞/组织来源的标准化多维模型。首先,我们证实了这种方法对于胰腺假胰岛的普遍适用性。接下来,我们将其应用于建立肾上腺皮质细胞系和患者来源的球体的适用性进行了转化,以建立来自恶性和良性肾上腺肿瘤的球体。我们还旨在开发牛来源的健康肾上腺类器官,并能够建立含有皮质和髓质来源细胞的类固醇生成活性类器官。总的来说,我们希望为基础研究、内分泌癌和肾上腺组织替代疗法开辟新的途径,因为我们展示了在内分泌(肿瘤)生物学方面的创新机制见解和个性化医学的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9138/9314441/2b7f2584ed1b/41419_2022_5096_Fig1_HTML.jpg

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