Innovative multidimensional models in a high-throughput-format for different cell types of endocrine origin

Area of Science:

• Endocrinology
• Regenerative Medicine
• Cancer Biology

Background:

• The adrenal gland integrates diverse signals and is central to the stress response, implicated in stress-related disorders.
• Regenerative approaches are lacking for endocrine diseases, unlike type-I diabetes, despite common adrenal tumor formation.
• Existing in vitro models lack high-throughput capabilities and relevant 3D structures for adrenal tumor heterogeneity.

Purpose of the Study:

• To develop standardized, multidimensional in vitro models for endocrine tissues, focusing on the adrenal gland.
• To create functional 3D organoid models from adrenal cell lines, patient tumors, and healthy bovine adrenal tissue.
• To explore new avenues for basic endocrine research, endocrine cancer studies, and adrenal tissue-replacement therapies.

Main Methods:

• Development of standardized multidimensional models in a multiwell format.
• Establishment of pancreatic pseudo-islets to confirm model applicability.
• Generation of spheroids from adrenocortical cell lines and patient-derived adrenal tumors (benign and malignant).
• Creation of steroidogenic active bovine adrenal organoids containing cortical and medullary cells.

Main Results:

• Confirmed applicability of the multiwell format for pancreatic pseudo-islets.
• Successfully established spheroids from various adrenal cell sources, including patient tumors.
• Developed functional bovine adrenal organoids with both cortical and medullary cell types.
• Demonstrated steroidogenic activity in the developed organoids.

Conclusions:

• The new multiwell-format enables the creation of standardized 3D endocrine models.
• These models offer potential for mechanistic insights into endocrine (tumor) biology and personalized medicine.
• The developed organoids pave the way for innovative research in endocrine cancer and adrenal tissue-replacement therapies.