TABLE 2.
Guidelines for co-culture design and features to include when reporting; a check-list. A summary of the three key aspects identified for co-culture model construction and a fourth key aspect describing model evaluation for validation. Each key aspect is itemized with pertinent considerations for co-culture model design as well as a designation on features that need reported to contextualize co-culture findings.
| Key aspects | Considerations | Report |
|---|---|---|
| i) Cell Types and interactions | Cancer cell | Species and tissue background |
| Confirm cell-specific characteristics | ||
| Confirm cell culture purity (no contamination) | ||
| Stromal cell type(s) | Species (if different, xeno-co-culture), tissue background and cell type | |
| Confirm cell-specific characteristics | ||
| Confirm cell culture purity (no contamination) | ||
| Juxtacrine/Paracrine Interactions | Direct or indirect co-culture | |
| How to identify cell types later, if required? | Any cell modifications performed, markers used | |
| ii) Physical arrangement and ECM context for each cell type | Dimensionality | Whether 2D, 3D or a combination |
| Physical cell context; Mechanotransduction | Description of co-culture architecture. Culture plastic, membrane, spheroid/tumor organoid, Scaffold (free) details | |
| ECM biochemical context | Description of chemical background of the co-culture; Inert or active? | |
| iii) Media | Does the media support the cells? | Effect of co-culture media selection on mono-cultured cell types included |
| Does the media influence relevant signaling? | Appropriate control conditions; consider different media for comparison—is effect dependent on particular medium? | |
| Media exchange (Microfluidics) | Static or dynamic media regimen; description | |
| Physical characteristics (Such as pressure, flow rate) | ||
| Body-on-a-chip; serial chambers and order, potential conditioned media effects of preceding chamber | ||
| iv) Validation | How well does the model perform? | How do adapted models compare to existing in vitro models? |
| For models with no existing in vitro comparison; assess by comparison to in vivo situation | ||
| Predictive capacity and translation | Do model results make predictions that can be assessed in vivo? How do these compare? |