Transplantation of porcine adrenal spheroids for the treatment of adrenal insufficiency.

IF 4.3 3区 材料科学 Q1 ENGINEERING, ELECTRICAL & ELECTRONIC
ACS Applied Electronic Materials Pub Date : 2023-09-01 Epub Date: 2023-08-07 DOI:10.1111/xen.12819
Maria Malyukov, Evgeny Gelfgat, Gerard Ruiz-Babot, Janine Schmid, Susann Lehmann, Giatgen Spinas, Felix Beuschlein, Constanze Hantel, Nicole Reisch, Peter P Nawroth, Stefan R Bornstein, Charlotte Steenblock, Barbara Ludwig
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Abstract

Primary adrenal insufficiency is a life-threatening disorder, which requires lifelong hormone replacement therapy. Transplantation of xenogeneic adrenal cells is a potential alternative approach for the treatment of adrenal insufficiency. For a successful outcome of this replacement therapy, transplanted cells should provide adequate hormone secretion and respond to adrenal physiological stimuli. Here, we describe the generation and characterization of primary porcine adrenal spheroids capable of replacing the function of adrenal glands in vivo. Cells within the spheroids morphologically resembled adult adrenocortical cells and synthesized and secreted adrenal steroid hormones in a regulated manner. Moreover, the embedding of the spheroids in alginate led to the formation of cellular elongations of steroidogenic cells migrating centripetally towards the inner part of the slab, similar to zona Fasciculata cells in the intact organ. Finally, transplantation of adrenal spheroids in adrenalectomized SCID mice reversed the adrenal insufficiency phenotype, which significantly improved animals' survival. Overall, such adrenal models could be employed for disease modeling and drug testing, and represent the first step toward potential clinical trials in the future.

猪肾上腺球体移植治疗肾上腺功能不全。
原发性肾上腺功能不全是一种危及生命的疾病,需要终生进行激素替代治疗。异种肾上腺细胞移植是治疗肾上腺功能不全的一种潜在的替代方法。为了这种替代疗法的成功结果,移植细胞应该提供足够的激素分泌并对肾上腺生理刺激做出反应。在此,我们描述了能够在体内取代肾上腺功能的原代猪肾上腺球体的产生和表征。球体内的细胞在形态上类似于成年肾上腺皮质细胞,并以调节的方式合成和分泌肾上腺类固醇激素。此外,将球体包埋在藻酸盐中导致类固醇生成细胞的细胞延伸形成,向板的内部向心迁移,类似于完整器官中的筋膜带细胞。最后,在肾上腺切除的SCID小鼠中移植肾上腺球体逆转了肾上腺功能不全表型,显著提高了动物的生存率。总的来说,这种肾上腺模型可以用于疾病建模和药物测试,并代表着未来潜在临床试验的第一步。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
7.20
自引率
4.30%
发文量
567
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