ArticleScientific reports2020
Development of a tunable method to generate various three-dimensional microstructures by replenishing macromolecules such as extracellular matrix components and polysaccharides.
Article in Scientific reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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14 citing papers in PubMed.
- An animal component-free bioprocess for synthesizing 3D human matrix scaffolds using mesenchymal stromal cells.Frontiers in cell and developmental biology · 2026Article
- Subaqueous acoustic pressure system based one day heterotypic pseudo-islet spheroid formation with adipose derived stem cells for graft survival-related function enhancement.Bioactive materials · 2025Article
- Review
- Enhancing therapeutic efficacy through degradation of endogenous extracellular matrix in primary breast tumor spheroids.The FEBS journal · 2025Article
- Extracellular matrix modulates the spatial hepatic features in hepatocyte-like cells derived from human embryonic stem cells.Stem cell research & therapy · 2023Article
- Engineered biomaterials to guide spheroid formation, function, and fabrication into 3D tissue constructs.Acta biomaterialia · 2023Review
- Rapid and Stable Formation Method of Human Astrocyte Spheroid in a High Viscous Methylcellulose Medium and Its Functional Advantages.Bioengineering (Basel, Switzerland) · 2023Article
- Three-Dimensional Spheroids for Cancer Research.Methods in molecular biology (Clifton, N.J.) · 2023Article
- 3D bioprinting of dECM-incorporated hepatocyte spheroid for simultaneous promotion of cell-cell and -ECM interactions.Frontiers in bioengineering and biotechnology · 2023Article
- Optimization of 3D-aggregated spheroid model (3D-ASM) for selecting high efficacy drugs.Scientific reports · 2022Article
- Soluble ECM promotes organotypic formation in lung alveolar model.Biomaterials · 2022Article
- Constructing biomimetic liver models through biomaterials and vasculature engineering.Regenerative biomaterials · 2022Review
- The ECM: To Scaffold, or Not to Scaffold, That Is the Question.International journal of molecular sciences · 2021Review
- Three-dimensional microscale hanging drop arrays with geometric control for drug screening and live tissue imaging.Science advances · 2021Article
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5 authors.
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Abstract
Multicellular spheroids (spheroids) are expected to be a promising approach to mimic in vivo organ functions and cell microenvironments. However, conventional spheroids do not fully consider the existence of extracellular matrices (ECMs). In this study, we developed a tunable method for replenishing macromolecules, including ECM components and polysaccharides, into spheroids without compromising cell viability by injecting a microvolume cell suspension into a high density of methylcellulose dissolved in the culture medium. Adjusting the ECM concentration in the cell suspension enabled the generation of different three-dimensional microstructures, such as "ECM gel capsules", which contained individually separated cells, and "ECM-loaded spheroids", which had thin ECM layers between cells. ECM-loaded spheroids with a 30-fold dilution of Matrigel (0.3 mg/ml) showed significantly higher albumin secretion than control spheroids composed of Hep G2 or HuH-7 cells. Additionally, the expression levels of major CYP genes were decreased in ECM gel capsules with undiluted Matrigel (9 mg/ml) compared to those in control spheroids. However, 0.3 mg/ml Matrigel did not disrupt gene expression. Furthermore, cell polarity associated with tight junction proteins (ZO-1 and Claudin-1) and the transporter protein MRP2 was markedly induced by using 0.3 mg/ml Matrigel. Thus, high-performance three-dimensional tissues fabricated by this method are applicable to increasing the efficiency of drug screening and to regenerative medicine.
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