University Hospital Carl Gustav Carus, Dept. of Medicine III, Technische Universität Dresden, Dresden, Germany.
Centre for Endocrinology, William Harvey Research Institute, Queen Mary University of London, London, United Kingdom.
PLoS One. 2018 Mar 29;13(3):e0194643. doi: 10.1371/journal.pone.0194643. eCollection 2018.
Encapsulation of primary bovine adrenocortical cells in alginate is an efficacious model of a bioartificial adrenal cortex. Such a bioartificial adrenal cortex can be used for the restoration of lost adrenal function in vivo as well as for in vitro modeling of the adrenal microenvironment and for investigation of cell-cell interactions in the adrenals. The aim of this work was the optimization of a bioartificial adrenal cortex, that is the generation of a highly productive, self-regenerating, long-term functioning and immune tolerant bioartificial organ. To achieve this, it is necessary that adrenocortical stem and progenitor cells are present in the bioartificial gland, as these undifferentiated cells play important roles in the function of the mature gland. Here, we verified the presence of adrenocortical progenitors in cultures of bovine adrenocortical cells, studied the dynamics of their appearance and growth and determined the optimal time point for cell encapsulation. These procedures increased the functional life span and reduced the immunogenicity of the bioartificial adrenal cortex. This model allows the use of the luteinizing hormone-releasing hormone (LHRH) agonist triptorelin, the neuropeptide bombesin, and retinoic acid to alter cell number and the release of cortisol over long periods of time.
将牛肾上腺皮质细胞封装在藻酸盐中是生物人工肾上腺皮质的有效模型。这种生物人工肾上腺皮质可用于恢复体内丧失的肾上腺功能,以及体外模拟肾上腺微环境,并研究肾上腺中的细胞-细胞相互作用。这项工作的目的是优化生物人工肾上腺皮质,即生成一种高产、自我再生、长期功能和免疫耐受的生物人工器官。为了实现这一目标,生物人工腺体中必须存在肾上腺皮质干细胞和祖细胞,因为这些未分化细胞在成熟腺体的功能中起着重要作用。在这里,我们验证了牛肾上腺皮质细胞培养物中存在肾上腺皮质祖细胞,研究了它们出现和生长的动态,并确定了细胞封装的最佳时间点。这些程序增加了生物人工肾上腺皮质的功能寿命并降低了其免疫原性。该模型允许使用黄体生成素释放激素(LHRH)激动剂曲普瑞林、神经肽 bombesin 和维甲酸来长时间改变细胞数量和皮质醇的释放。