A Dual-Chamber Tumor–Cardiac Model Measures Morphological Responses to Chemotherapy
Separate breast-cancer and cardiac cell-line tissues maintained in a shared microfluidic platform changed shape after doxorubicin exposure. Automated image analysis also detected responses in a separate glioblastoma model, with cell size rather than cardiac function or direct survival as the main quantitative endpoint.
Two Tissues, One Culture Platform
A study led by the University of Texas at El Paso paired a HER2-positive breast-cancer tissue model with a cardiac cell-line tissue in a dual-chamber microfluidic device. The aim was to examine anticancer and cardiac responses within the same culture environment. A separate glioblastoma experiment tested whether the platform could support another tumor type.
The breast and cardiac constructs used SKBR3 and AC16 cells, respectively, encapsulated in separate collagen hydrogels. Each occupied its own chamber. The investigators compared the device with Transwell cultures, including cultures maintained alone and breast–cardiac cocultures. U87 glioblastoma cells were tested separately. These were established cell-line models, without patient-derived tumor material.
The final device was cast in a clear polymer using a mold made from a three-dimensional printed template. Collagen at 2 mg/mL supported cells seeded at 200,000 cells/mL. Fluorescence imaging on days 3 and 7 assessed tissue organization and lineage-associated markers: HER2 in breast-cancer cells, α-actinin in cardiac cells and nestin in U87 cells.
Automating a Morphological Readout
The Automated Image Analysis Python Script, or AIAPS, combined intensity thresholding, image erosion and watershed segmentation to identify cells and estimate their projected size. Although the source images were fluorescence z-stacks, the analysis operated on two-dimensional projections. Its diameter estimates therefore describe a projected contour rather than a complete three-dimensional cell shape.
For an initial comparison, the researchers analyzed fluorescent beads with both AIAPS and ImageJ/FIJI at several bead densities. Both methods returned diameters within the manufacturer’s broad nominal range of 1–10 μm, but their estimates differed significantly. This supported practical feature detection while leaving the two measurement methods distinguishable.
Tissue imaging used three biological specimens per condition and five z-stacks per specimen. By day 7, breast-cancer cell sizes had converged to approximately 30–40 μm without a significant difference between culture groups. U87 cell size also did not differ significantly between the device and Transwell at either time point, although size declined between days 3 and 7 within the device.
Drug Responses Depend on the Culture Setting
Doxorubicin was tested at 10 μM for 48 hours. Treated breast and cardiac tissues showed rounder cells, diminished clusters or disrupted networks. AC16 cell size decreased significantly in the device, whereas the corresponding Transwell comparison was not significant. SKBR3 size changed significantly across the tested culture conditions.
The separate U87 experiment compared 10 μM doxorubicin and 200 μM temozolomide for 48 hours after three days of culture. The Figure 6 caption reports a significant reduction in projected cell size with either treatment in the device. The Results text specifically describes a significant doxorubicin effect in the device that was absent in the Transwell comparison.
These observations establish that the culture setting can change the sensitivity of a morphological drug-response measurement. The study did not measure cardiac contraction, electrophysiology or a clinical cardiotoxicity outcome, and projected cell size was not a direct count of surviving cells. Its restricted dose testing also leaves concentration–response relationships unresolved. The next development step proposed by the authors is to combine patient-derived tumors and more advanced cardiac cells with broader drug testing and richer shape measurements.