Injectable therapeutic organoids using sacrificial hydrogels

Abstract

Organoids, by promoting self-organization of cells into native-like structures, are becoming widespread in drug-screening technologies, but have so far been used sparingly for cell therapy as current approaches for producing self-organized cell clusters lack scalability or reproducibility in size and cellular organization. We introduce a method of using hydrogels as sacrificial scaffolds, which allow cells to form self-organized clusters followed by gentle release, resulting in highly reproducible multicellular structures on a large scale. We demonstrated this strategy for endothelial cells and mesenchymal stem cells to self-organize into blood-vessel units, which were injected into mice using hypodermic needles, and observed in real time to rapidly form perfusing vasculature. As cell therapy transforms into a new class of therapeutic modality, this simple method - by making use of the dynamic nature of hydrogels - could offer high yields of self-organized multicellular aggregates with reproducible sizes and cellular architectures.