Defined Alginate Hydrogels Support Spinal Cord Organoid Derivation, Maturation, and Modeling of Spinal Cord Diseases

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Defined Alginate Hydrogels Support Spinal Cord Organoid Derivation, Maturation, and Modeling of Spinal Cord Diseases
Title:
Defined Alginate Hydrogels Support Spinal Cord Organoid Derivation, Maturation, and Modeling of Spinal Cord Diseases
Journal Title:
Advanced Healthcare Materials
Publication Date:
11 December 2022
Citation:
Chooi, W. H., Ng, C. Y., Ow, V., Harley, J., Ng, W., Hor, J., Low, K. E., Malleret, B., Xue, K., & Ng, S. (2022). Defined Alginate Hydrogels Support Spinal Cord Organoid Derivation, Maturation, and Modeling of Spinal Cord Diseases. Advanced Healthcare Materials, 12(9). Portico. https://doi.org/10.1002/adhm.202202342
Abstract:
AbstractIn the process of generating organoids, basement membrane extracts or Matrigel are often used to encapsulate cells but they are poorly defined and contribute to reproducibility issues. While defined hydrogels are increasingly used for organoid culture, the effects of replacing Matrigel with a defined hydrogel on neural progenitor growth, neural differentiation, and maturation within organoids are not well‐explored. In this study, the use of alginate hydrogels as a Matrigel substitute in spinal cord organoid generation is explored. It is found that alginate encapsulation reduces organoid size variability by preventing organoid aggregation. Importantly, alginate supports neurogenesis and gliogenesis of the spinal cord organoids at a similar efficiency to Matrigel, with mature myelinated neurons observed by day 120. Furthermore, using alginate leads to lower expression of non‐spinal markers such as FOXA2, suggesting better control over neural fate specification. To demonstrate the feasibility of using alginate‐based organoid cultures as disease models, an isogenic pair of induced pluripotent stem cells discordant for the ALS‐causing mutation TDP43G298S is used, where increased TDP43 mislocalization in the mutant organoids is observed. This study shows that alginate is an ideal substitute for Matrigel for spinal cord organoid derivation, especially when a xeno‐free and fully defined 3D culture condition is desired.
License type:
Publisher Copyright
Funding Info:
This research / project is supported by the National Research Foundation - NRF Fellowship
Grant Reference no. : NRF-NRFF2018-003

This research / project is supported by the A*STAR - Career Development Award
Grant Reference no. : 202D8054
Description:
This is the peer reviewed version of the following article: Chooi, W. H., Ng, C. Y., Ow, V., Harley, J., Ng, W., Hor, J., Low, K. E., Malleret, B., Xue, K., & Ng, S. (2022). Defined Alginate Hydrogels Support Spinal Cord Organoid Derivation, Maturation, and Modeling of Spinal Cord Diseases. Advanced Healthcare Materials, 12(9). Portico. https://doi.org/10.1002/adhm.202202342, which has been published in final form at doi.org/10.1002/adhm.202202342. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. This article may not be enhanced, enriched or otherwise transformed into a derivative work, without express permission from Wiley or by statutory rights under applicable legislation. Copyright notices must not be removed, obscured or modified. The article must be linked to Wiley’s version of record on Wiley Online Library and any embedding, framing or otherwise making available the article or pages thereof by third parties from platforms, services and websites other than Wiley Online Library must be prohibited.
ISSN:
2192-2640
2192-2659
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