功能性血管化小鼠甲状腺构建体的生物打印。

Bioprinting of a functional vascularized mouse thyroid gland construct.

作者信息

Bulanova Elena A, Koudan Elizaveta V, Degosserie Jonathan, Heymans Charlotte, Pereira Frederico DAS, Parfenov Vladislav A, Sun Yi, Wang Qi, Akhmedova Suraya A, Sviridova Irina K, Sergeeva Natalia S, Frank Georgy A, Khesuani Yusef D, Pierreux Christophe E, Mironov Vladimir A

机构信息

Laboratory for Biotechnological Research '3D Bioprinting Solutions', Moscow 115409, Russia.

出版信息

Biofabrication. 2017 Aug 18;9(3):034105. doi: 10.1088/1758-5090/aa7fdd.

Abstract

Bioprinting can be defined as additive biofabrication of three-dimensional (3D) tissues and organ constructs using tissue spheroids, capable of self-assembly, as building blocks. The thyroid gland, a relatively simple endocrine organ, is suitable for testing the proposed bioprinting technology. Here we report the bioprinting of a functional vascularized mouse thyroid gland construct from embryonic tissue spheroids as a proof of concept. Based on the self-assembly principle, we generated thyroid tissue starting from thyroid spheroids (TS) and allantoic spheroids (AS) as a source of thyrocytes and endothelial cells (EC), respectively. Inspired by mathematical modeling of spheroid fusion, we used an original 3D bioprinter to print TS in close association with AS within a collagen hydrogel. During the culture, closely placed embryonic tissue spheroids fused into a single integral construct, EC from AS invaded and vascularized TS, and epithelial cells from the TS progressively formed follicles. In this experimental setting, we observed formation of a capillary network around follicular cells, as observed during in utero thyroid development when thyroid epithelium controls the recruitment, invasion and expansion of EC around follicles. To prove that EC from AS are responsible for vascularization of the thyroid gland construct, we depleted endogenous EC from TS before bioprinting. EC from AS completely revascularized depleted thyroid tissue. The cultured bioprinted construct was functional as it could normalize blood thyroxine levels and body temperature after grafting under the kidney capsule of hypothyroid mice. Bioprinting of functional vascularized mouse thyroid gland construct represents a further advance in bioprinting technology, exploring the self-assembling properties of tissue spheroids.

摘要

生物打印可定义为使用能够自我组装的组织球状体作为构建模块,对三维(3D)组织和器官构建体进行增材生物制造。甲状腺是一个相对简单的内分泌器官,适合用于测试所提出的生物打印技术。在此,我们报告了从胚胎组织球状体生物打印出功能性血管化小鼠甲状腺构建体,作为概念验证。基于自我组装原理,我们分别从甲状腺球状体(TS)和尿囊球状体(AS)生成甲状腺组织,AS作为甲状腺细胞和内皮细胞(EC)的来源。受球状体融合数学模型的启发,我们使用一台原创的3D生物打印机在胶原水凝胶中将TS与AS紧密结合打印。在培养过程中,紧密放置的胚胎组织球状体融合成一个单一的整体构建体,来自AS的EC侵入TS并使其血管化,来自TS的上皮细胞逐渐形成滤泡。在这个实验环境中,我们观察到滤泡细胞周围形成了毛细血管网络,这与子宫内甲状腺发育过程中甲状腺上皮控制滤泡周围EC的募集、侵入和扩张时所观察到的情况相同。为了证明来自AS的EC对甲状腺构建体的血管化负责,我们在生物打印前耗尽了TS中的内源性EC。来自AS的EC使耗尽的甲状腺组织完全重新血管化。培养的生物打印构建体具有功能,因为在移植到甲状腺功能减退小鼠的肾被膜下后,它可以使血液甲状腺素水平和体温恢复正常。功能性血管化小鼠甲状腺构建体的生物打印代表了生物打印技术的进一步进展,探索了组织球状体的自我组装特性。

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