1 Thyroid Disease Diagnosis and Treatment Center; School of Medicine, Zhejiang University, Hangzhou, P.R. China.
2 Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Division of Hepatobiliary and Pancreatic Surgery; School of Medicine, Zhejiang University, Hangzhou, P.R. China.
Thyroid. 2019 Jan;29(1):142-152. doi: 10.1089/thy.2018.0068. Epub 2018 Dec 18.
Hypothyroidism is a common hormone deficiency condition. Regenerative medicine approaches, such as a bioengineered thyroid, have been proposed as potential therapeutic alternatives for patients with hypothyroidism. This study demonstrates a novel approach to generate thyroid grafts using decellularized rat thyroid matrix.
Isolated rat thyroid glands were perfused with 1% sodium dodecyl sulfate to generate a decellularized thyroid scaffold. The rat thyroid scaffold was then recellularized with rat thyroid cell line to reconstruct the thyroid by perfusion seeding technique. As a pilot study, the decellularized rat thyroid scaffold was perfused with human-derived thyrocytes and parathyroid cells.
The decellularization process retained the intricate three-dimensional microarchitecture with a perfusable vascular network and native extracellular matrix components, allowing efficient reseeding of the thyroid matrix with the FRTL-5 rat thyroid cell line generating three-dimensional follicular structures in vitro. In addition, the recellularized thyroid showed successful cellular engraftment and thyroid-specific function, including synthesis of thyroglobulin and thyroid peroxidase. Moreover, the decellularized rat thyroid scaffold could further be recellularized with human-derived thyroid cells and parathyroid cells to reconstruct a humanized bioartificial endocrine organ, which maintained expression of critical genes such as thyroglobulin, thyroid peroxidase, and parathyroid hormone.
These findings demonstrate the utility of a decellularized thyroid extracellular matrix scaffold system for the development of functional, bioengineered thyroid tissue, which could potentially be used to treat hypothyroidism.
甲状腺功能减退症是一种常见的激素缺乏症。再生医学方法,如生物工程甲状腺,已被提议作为甲状腺功能减退症患者的潜在治疗替代方法。本研究展示了一种使用脱细胞大鼠甲状腺基质生成甲状腺移植物的新方法。
用 1%十二烷基硫酸钠对分离的大鼠甲状腺进行灌流,以生成脱细胞甲状腺支架。然后通过灌流接种技术用大鼠甲状腺细胞系使大鼠甲状腺支架再细胞化,以重建甲状腺。作为初步研究,用来源于人甲状腺细胞和甲状旁腺细胞对脱细胞大鼠甲状腺支架进行灌流。
脱细胞过程保留了复杂的三维微观结构,具有可灌注的血管网络和天然细胞外基质成分,允许用 FRTL-5 大鼠甲状腺细胞系有效地对甲状腺基质进行再细胞化,在体外生成三维滤泡结构。此外,再细胞化的甲状腺显示出成功的细胞植入和甲状腺特异性功能,包括甲状腺球蛋白和甲状腺过氧化物酶的合成。此外,脱细胞大鼠甲状腺支架可以进一步与来源于人甲状腺细胞和甲状旁腺细胞进行再细胞化,以重建具有人源化生物人工内分泌器官,维持关键基因如甲状腺球蛋白、甲状腺过氧化物酶和甲状旁腺激素的表达。
这些发现证明了脱细胞甲状腺细胞外基质支架系统在功能性生物工程甲状腺组织开发中的实用性,这可能可用于治疗甲状腺功能减退症。