Integrating Electrogenic Cells into Organoid Structures with Electrically Conductive Scaffolds Augments Function and Cell Therapy Production

Engineered cell therapies have the incredible potential to replace cells lost or damaged in disease states including cellular biofactories that effectively serve as a renewable source of therapeutic biomolecules (in vivo pharmacy). Harnessing the power of these cell therapies critically depends on our ability to integrate the cells themselves into configurations that facilitate therapeutic biomolecule production and long-term function of the cells after implantation. Here, we explore the impact of planar vs. 3D organoid configurations integrated with electrically conductive scaffolds (e-scaffolds) on the production of melatonin as well as the function of electrogenic cells in a network. We found that when melatonin producing pinealocytes are integrated into organoid structures with support cells such as astrocytes, their melatonin production is greatly augmented. The presence of e-scaffolds dispersed throughout these organoids further improve melatonin production, potentially serving as a substrate that enhances cell-to-cell communication. To further investigate how e-scaffolds alter electrical properties of 3D structures, we turned to organoids comprising cortical neurons and astrocytes. Using a combination of multi-electrode arrays and Ca⁺⁺ imaging we show improved connectivity and neural activity. Finally, towards in vivo cell therapy applications, we show that 3D pineal structures encapsulated in a biocarrier promote melatonin production over days when implanted in rats. Together, these data suggest that when cell therapy producing cells are integrated with support cells and e-scaffolds into organoid structures, they have increased therapy production characteristics with potential for enhanced electrical control of therapy production.