Recently engineered 3-dimensional (3D) endocrine patient-derived organoids from medullary thyroid carcinoma (MTC), papillary thyroid carcinoma (PTC), and adrenocortical carcinoma (ACC) have potential applications in endocrine oncoimnunology, according to a recently published study in Surgery.

The recent development of 3D patient-derived organoid cancer models has many potential medical applications, like serving as preclinical tumor models for treatment development, Naira Baregamian, MD, MMS, of Vanderbilt University Medical Center in Nashville, Tennessee, and colleagues noted.  

Unfortunately, several obstacles, such as the terminal differentiation of endocrine cells, hormone secretion, and the difficulty of replication of physiological feedback loops in culture, have prevented the development of 3D organoid models of endocrine cells, they added.


Continue Reading

Read more about MTC therapies

“There is an urgent need for the development and use of endocrine tumor organoid platforms to model several endocrine diseases, including malignancy,” the study authors wrote.

Therefore, the authors aimed to engineer functionally intact 3D models of thyroid and adrenal malignancies in the hope of contributing to the rapid advancement of endocrine research using 3D culture technologies. 

Samples of endocrine tissues were collected from the operating room at the time of resection using sterile fine needle aspiration. The collected samples were stained with hematoxylin-eosin and underwent posterior immunohistochemical analysis for endocrine markers and imaging.

After undergoing centrifugation, the cells were suspended in previously prepared complete organoid media. Following organoid formation, the samples were cryopreserved. Before cryopreservation, organoids underwent successful culture passages at least 3 times.

From a morphologic standpoint, all of the cultured organoids replicated their respective tumor microenvironment. Furthermore, all expressed organ-specific markers. Notably, MTC organoids required a longer culture time than PTC and ACC organoids.

Transmission electron microscopy revealed the presence of cellular structures typical of endocrine cells, such as secretory granules and a pronounced Golgi apparatus. Fortunately, all organoid models maintained hormonal functionality on 3D cultures.

“Using endocrine organoid models for endocrine oncoimmunology applications provides an invaluable preclinical route for modeling the complexities of endocrine tumors in vitro for drug development and immune response modulation,” the authors concluded. 

Reference

Baregamian N, Sekhar K, Krystofiak E, et al. Engineering functional 3-dimensional patient-derived endocrine organoids for broad multiplatform applications. Surgery. Published online November 16, 2022. doi:10.1016/j.surg.2022.09.027