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 E. Goldenberg,
Nirali Sampat,
Tetsuhiro Harimoto,
Danielle R. Bajakian,
Brian M. Gillette,
Samuel K. Sia
Affiliations
Ninna S. Rossen
Department of Biomedical Engineering, Columbia University, 351 Engineering Terrace, 1210 Amsterdam Avenue, New York, NY 10027, USA; Biotech Research & Innovation Centre, University of Copenhagen, University of Copenhagen, Ole MaaløesVej 5, 2200 Copenhagen N, Denmark; Department of Radiation Oncology, Stanford University, 269 Campus Drive, Palo Alto, CA 94305, USA
Priya N. Anandakumaran
Department of Biomedical Engineering, Columbia University, 351 Engineering Terrace, 1210 Amsterdam Avenue, New York, NY 10027, USA
Rafael zur Nieden
Department of Biomedical Engineering, Columbia University, 351 Engineering Terrace, 1210 Amsterdam Avenue, New York, NY 10027, USA
Kahmun Lo
Department of Biomedical Engineering, Columbia University, 351 Engineering Terrace, 1210 Amsterdam Avenue, New York, NY 10027, USA
Wenjie Luo
Department of Biomedical Engineering, Columbia University, 351 Engineering Terrace, 1210 Amsterdam Avenue, New York, NY 10027, USA
Christian Park
Department of Biomedical Engineering, Columbia University, 351 Engineering Terrace, 1210 Amsterdam Avenue, New York, NY 10027, USA
Chuqiao Huyan
Department of Biomedical Engineering, Columbia University, 351 Engineering Terrace, 1210 Amsterdam Avenue, New York, NY 10027, USA
Qinyouen Fu
Department of Biomedical Engineering, Columbia University, 351 Engineering Terrace, 1210 Amsterdam Avenue, New York, NY 10027, USA
Ziwei Song
Department of Biomedical Engineering, Columbia University, 351 Engineering Terrace, 1210 Amsterdam Avenue, New York, NY 10027, USA
Rajinder P. Singh-Moon
Department of Biomedical Engineering, Columbia University, 351 Engineering Terrace, 1210 Amsterdam Avenue, New York, NY 10027, USA
Janice Chung
Department of Biomedical Engineering, Columbia University, 351 Engineering Terrace, 1210 Amsterdam Avenue, New York, NY 10027, USA
Jennifer E. Goldenberg
Department of Biomedical Engineering, Columbia University, 351 Engineering Terrace, 1210 Amsterdam Avenue, New York, NY 10027, USA
Nirali Sampat
Department of Biomedical Engineering, Columbia University, 351 Engineering Terrace, 1210 Amsterdam Avenue, New York, NY 10027, USA
Tetsuhiro Harimoto
Department of Biomedical Engineering, Columbia University, 351 Engineering Terrace, 1210 Amsterdam Avenue, New York, NY 10027, USA
Danielle R. Bajakian
Department of Surgery - Division of Vascular Surgery and Endovascular Interventions, Columbia University Medical Center, Herbert Irving Pavilion, 161 Fort Washington Avenue, New York, NY 10032, USA
Brian M. Gillette
Department of Biomedical Engineering, Columbia University, 351 Engineering Terrace, 1210 Amsterdam Avenue, New York, NY 10027, USA
Samuel K. Sia
Department of Biomedical Engineering, Columbia University, 351 Engineering Terrace, 1210 Amsterdam Avenue, New York, NY 10027, USA; Corresponding author
Summary: 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.
