Injectable Therapeutic Organoids Using Sacrificial Hydrogels
Ninna S. Rossen, Priya N. Anandakumaran, Rafael zur Nieden, Kahmun Lo, Wenjie Luo, Christian Park, Chuqiao Huyan, Qinyouen Fu, Ziwei Song, Rajinder P. Singh‐Moon, Janice Chung, Jennifer Goldenberg, Nirali Sampat, Tetsuhiro Harimoto, Danielle Bajakian, Brian M. Gillette, Samuel K. Sia
Abstract
Organoids are becoming widespread in drug-screening technologies but have 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, and rapidly formed perfusing vasculature. Moreover, in a mouse model of peripheral artery disease, intramuscular injections of blood-vessel units resulted in rapid restoration of vascular perfusion within seven days. 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.