Table 2.
Selected three-dimensional models for rheumatoid arthritis.
| Model | Cells | Applications | Limitations |
|---|---|---|---|
| Spheroids | Fibroblasts [49] | Analysis of phenotypic characteristics of normal and hyperplastic synovium | Simplistic The stiffness and absorption rate of these natural matrices cannot be adjusted Lack of fluid flow perfusion Accumulation of metabolites Low reproducibility |
| Fibroblasts [50] | Determine effects of proinflammatory cytokines | ||
| Fibroblasts from patients with RA Monocytes CD14+ [51] |
Analysis of hyperplasia Alteration of phenotype in macrophages Determination of the effects of proinflammatory cytokines |
||
| Primary chondrocytes Differentiated stem cells [8] | Test of biological anti-inflammatory drugs | ||
| Fibroblasts Endothelial cells [52] |
Synovial angiogenesis Effect of NF-kB signaling Test of inhibitors of signaling pathways |
||
| Primary synoviocytes Peripheral blood mononuclear cell (PBMC) Mesenchymal stromal cell (MSC) [53] |
Formation of de novo vascular structures in the context of inflammation | ||
| Scaffold | Chondrocytes Fibroblasts [54] |
Destruction of cartilage Gene expression To determine the role of genes in the pathogenesis |
Reductionist No compound and oxygen gradients Lack of mechanical stimuli, such as tension and compression |
| Chondrocytes Fibroblasts [55] |
Pannus model Investigation of pathogenesis High-throughput drug screening |
||
| Macrophages Primary chondrocytes Fibroblasts [56] |
Simulate pathological characteristics of cartilage with RA Determine alterations in chondrocyte phenotype Test drugs |
||
| Synovial fibroblasts Vascular endothelial cells [57] |
Pannus model applying 3D printing technique Drug testing |
||
| Microfluidics | Primary synoviocytes [1] | Monitor the onset and progression of synovial inflammatory responses | Challenging Difficult to operate, control, standardize and scale Difficult to adapt to high throughput screening Lack of biomechanical stimulation |
| Fibroblasts Osteoclasts [58] |
Predict fibroblast migration to bone cells Test drugs |
||
| Monocytes Primary chondrocytes [59] |
Representation of healthy and disease scenario Test the therapeutic efficacy of possible treatments |
||
| Primary synoviocytes Primary chondrocytes [60] |
Joint-on-a-chip Simulation of crosstalk between synovial and chondral organoids |