Related Experiment Video
Updated: Aug 6, 2026
Reconstituting Cytoarchitecture and Function of Human Epithelial Tissues on an Open-Top Organ-Chip
Published on: February 17, 2023
Multi-cell-component cartilage organoids simulate intercellular microstress, hypoxic microenvironment, and
Zhengchao Wang1,2,3,4, Pengfei Zhu2,3,4,5, Hongmei Li6
1Department of Sports Medicine, Wuhan Fourth Hospital, Wuhan, China.
Introduction:
In cartilage-related studies, the existing in vitro cartilage models often fail to simulate the complex pathophysiology involving a hypoxic microenvironment, abnormal intercellular mechanical stress (microstress), and pathological crosstalk between chondrocytes and vascular endothelial cells. he aim of this study was to develop and validate a novel, simplified multi-cell-component cartilage organoid model capable of mimicking these three key OA-related features in vitro, using readily available cell lines.
Methods:
Organoids were constructed using SW1353 chondrocytes and HMEC-1 endothelial cell lines within low-adhesion grid microchambers. A monosodium iodoacetate (MIA)-induced OA model was developed. Histological and immunofluorescence analyses of the organoids were conducted to examine markers of matrix metabolism, cytoskeletal and intercellular microstress, hypoxic microenvironment, and chondrocyte -endothelial crosstalk. The organoid features were compared with those of standard 2D cell cultures and in vivo cartilages.
Results:
The multi-cell-component organoids successfully recapitulated critical in vivo features. They exhibited MIA-induced F-actin reorganization and PIEZO1 upregulation, developed a hypoxic core with elevated hypoxia-inducible factor 1-alpha (HIF-1α) levels, and formed an endothelial shell that invasively disrupted the chondrocyte core upon MIA treatment. This disruption was accompanied by the activation of vascular endothelial growth factor -NOTCH receptor 1 -delta-like ligand 4 (VEGF -NOTCH1 -DLL4) signaling, mirroring the pathological chondrocyte -endothelial crosstalk. Single-cell-component organoids simulated microstress-related changes but not hypoxia or chondrocyte -endothelial crosstalk.
Discussion:
The multi-cell-component cartilage organoids constructed from tumor-derived cell lines using low-adhesion grid microchambers partially simulated intercellular microstress, hypoxic microenvironment, and chondrocyte -endothelial crosstalk, which was similar to that observed in cartilages in vivo. These organoids provide a new strategy for conducting cartilage-related studies in vitro.
