Injectable Therapeutic Organoids Using Sacrificial Hydrogels
Open accessPublished version of a preprint
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.
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Organoid types grown in alginate include human lung, human brain, murine intestinal, human intestinal, human pancreatic, and human and murine vascular.
“Organoid types grown in alginate include human lung99,100, human brain101, murine intestinal102, human intestinal102,103, human pancreatic104, and human and murine vascular105.”
From Towards organoid culture without Matrigel (2021) · cites this paper as [105]
Several laboratories have grown a wide range of organoids in polysaccharides such as alginate or alginate-chitosan mixtures.
“In addition to organoids grown in naturally-derived proteins, several laboratories have grown a wide range of organoids in polysaccharides such as alginate or alginate-chitosan mixtures.”
From Towards organoid culture without Matrigel (2021) · cites this paper as [105]
Murine and human vascular organoids developed in a non-functionalized alginate setting.
“Rossen and colleagues demonstrated the development of murine and human vascular organoids in a non-functionalized alginate setting105.”
From Towards organoid culture without Matrigel (2021) · cites this paper as [105]
There have been a number of studies showing that organoids can be grown on unmodified surfaces such as alginate, but this requires more research.
“There have been a number of studies showing that organoids can be grown on unmodified surfaces such as alginate, but this requires more research103,105,110,175,183.”
From Towards organoid culture without Matrigel (2021) · cites this paper as [105]
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References 69 · Cited by 36
- Authors
- Rossen, N. S., Anandakumaran, P. N., zur Nieden, R., Lo, K., Luo, W., Park, C., Huyan, C., Fu, Q., Song, Z., Singh-Moon, R. P., Chung, J., Goldenberg, J. E., Sampat, N., Harimoto, T., Bajakian, D. R., Gillette, B. M., & Sia, S. K.
- Affiliations
- University of Copenhagen (DK)
- Columbia University (US)
- Columbia University Irving Medical Center (US)
- Corresponding author
- Sia, Samuel K.
- ORCID
- Venue
- iScience
- Publisher
- Elsevier BV
- Published
- 2020-05
- Volume
- 23
- Issue
- 5
- Pages
- 101052
- ISSN
- 2589-0042 (ISSN-L)
- PMC
- PMC7191221
- OpenAlex
- W3015536249
- Cited by
- 36
- References
- 69
- Citations by year
- 2026: 6 · 2025: 8 · 2024: 2 · 2023: 5 · 2022: 4 · 2021: 9 · 2020: 2
- FWCI
- 1.57
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- iScience (publishedVersion, cc-by-nc-nd)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Novo Nordisk Fonden (NNF15OC0015218)
- National Institutes of Health (5R01HL141935, R01HL095477-05R01)
- Columbia University
- Villum Fonden
- Studienstiftung des Deutschen Volkes
- Gerhard C. Starck Stiftung
- Topics
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Hydrogels: synthesis, properties, applications
- Keywords
- cell therapy, endothelial cells, mesenchymal stem cells, vascular perfusion, peripheral arterial disease, intramuscular injection
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