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Article

Targeting Conserved Pathways in 3D Spheroid Formation of Diverse Cell Types for Translational Application: Enhanced Functional and Antioxidant Capacity

by
Chia-Chi Chang
1,2,
Shih-Sheng Jiang
3,
Fang-Yu Tsai
3,
Pei-Ju Hsu
2,
Chen-Chan Hsieh
2,
Li-Tzu Wang
4,
Men-Luh Yen
4 and
B. Linju Yen
1,2,*
1
Graduate Institute of Life Sciences, National Defense Medical Center (NDMC), Taipei 114, Taiwan
2
Regenerative Medicine Research Group, Institute of Cellular & System Medicine, National Health Research Institutes (NHRI), Zhunan 350, Taiwan
3
National Institute of Cancer Research, NHRI, Zhunan 350, Taiwan
4
Department of Obstetrics/Gynecology, National Taiwan University (NTU) Hospital & College of Medicine, Taipei 100, Taiwan
*
Author to whom correspondence should be addressed.
Cells 2023, 12(16), 2050; https://doi.org/10.3390/cells12162050
Submission received: 8 July 2023 / Revised: 3 August 2023 / Accepted: 9 August 2023 / Published: 11 August 2023
(This article belongs to the Collection Advances in 3D Cell Culture)
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Abstract

Three-dimensional (3D) in vitro spheroid/organoid culture increasingly appears to better mimic physiological states than standard 2D systems. The biological consequence of 3D spheroids, however, differs for different cell types: for pluripotent embryonic stem cells (ESCs), differentiation and loss of stemness occur, while the converse is true for somatic and cancer cells. Despite such diverse consequences, there are likely conserved mechanisms governing 3D spheroid formation across cell types that are unknown but could be efficiently targeted for translational application. To elucidate such processes, we performed transcriptome analysis with functional validation on 2D- and 3D-cultured mouse ESCs, mesenchymal stromal/stem cells (MSCs), and cancer cells. At both the transcriptomic and functional levels, 3D spheroid formation resulted in commitment towards known cell-specific functional outcomes. Surprisingly in all cell types, downregulation of the cholesterol synthesis pathway was found during 3D spheroid formation, with modulation concomitantly affecting 3D spheroid formation and cell-specific consequences; similar results were seen with human cell types. Furthermore, improved antioxidant capacity after 3D spheroid formation across cell types was further enhanced with modulation of the pathway. These findings demonstrate the profound cell-specific consequences and the translational value of understanding conserved mechanisms across diverse cell types after 3D spheroid formation.
Keywords: three-dimensional (3D) spheroid formation; pluripotent stem cells; mesenchymal stem cells; cancer cells; cholesterol synthesis; cytoskeleton modification; antioxidant capacity three-dimensional (3D) spheroid formation; pluripotent stem cells; mesenchymal stem cells; cancer cells; cholesterol synthesis; cytoskeleton modification; antioxidant capacity
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MDPI and ACS Style

Chang, C.-C.; Jiang, S.-S.; Tsai, F.-Y.; Hsu, P.-J.; Hsieh, C.-C.; Wang, L.-T.; Yen, M.-L.; Yen, B.L. Targeting Conserved Pathways in 3D Spheroid Formation of Diverse Cell Types for Translational Application: Enhanced Functional and Antioxidant Capacity. Cells 2023, 12, 2050. https://doi.org/10.3390/cells12162050

AMA Style

Chang C-C, Jiang S-S, Tsai F-Y, Hsu P-J, Hsieh C-C, Wang L-T, Yen M-L, Yen BL. Targeting Conserved Pathways in 3D Spheroid Formation of Diverse Cell Types for Translational Application: Enhanced Functional and Antioxidant Capacity. Cells. 2023; 12(16):2050. https://doi.org/10.3390/cells12162050

Chicago/Turabian Style

Chang, Chia-Chi, Shih-Sheng Jiang, Fang-Yu Tsai, Pei-Ju Hsu, Chen-Chan Hsieh, Li-Tzu Wang, Men-Luh Yen, and B. Linju Yen. 2023. "Targeting Conserved Pathways in 3D Spheroid Formation of Diverse Cell Types for Translational Application: Enhanced Functional and Antioxidant Capacity" Cells 12, no. 16: 2050. https://doi.org/10.3390/cells12162050

APA Style

Chang, C.-C., Jiang, S.-S., Tsai, F.-Y., Hsu, P.-J., Hsieh, C.-C., Wang, L.-T., Yen, M.-L., & Yen, B. L. (2023). Targeting Conserved Pathways in 3D Spheroid Formation of Diverse Cell Types for Translational Application: Enhanced Functional and Antioxidant Capacity. Cells, 12(16), 2050. https://doi.org/10.3390/cells12162050

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