Abstract: With the rapid expansion of the field of 3D cultures and organoids, interest in their therapeutic use is growing. However, these innovative formats pose unique challenges for clinical translation as their physical and biological properties substantially differ from those of conventional single-cell-based products. Their handling imposes new constraints, such as much faster sedimentation, which must be addressed from the fill-and-finish stage to the final delivery procedure in the target region to ensure accurate dosing and precise cell placement. In this study, we present the development of a strategy to maintain homogeneity throughout the entire downstream process for the delivery of 3D neural microtissues as a cell therapy for Parkinson’s disease. This includes the development of a custom-made delivery solution. Various delivery methods were compared using in vitro tests. The final selected strategy was validated through in-use testing and led to successful engraftment in a non-human primate, with the presence of dopaminergic (DA) neurons observed 1 month after transplantation. The development approach described here holds potential for broader applications in other diseases and supports using next-generation cell therapies employing 3D formats.
