Q9 — Organ-on-a-Chip — Lung-on-a-Chip & Pulmonary Oedema Model

Theoretical 1 Real exam question — full text reproduced under IBO's CC BY-NC-SA 4.0 license

Cell Junctions, Extracellular Matrix & Cell Death Recombinant DNA & Biotechnology Techniques

Tissue engineering is trying to develop miniature blocks of tissue from multiple cell types using an approach called ‘organ-on-a-chip’. This technology enables in vitro testing of patient-specific effects of different drugs or treatments. Cells collected from a patient are first turned into induced pluripotent stem cells (iPSCs), then differentiated and seeded into specially designed chambers.

Figure 1. The endothelial barrier of the alveolus, showing epithelial cells, air space, interstitium, and endothelial cells against the blood capillary. Figure 1. The endothelial barrier of alveoli — epithelial cells facing air (alveolus), separated from endothelial cells facing blood (capillary) by a thin interstitium.

This ’lung-on-a-chip’ models pulmonary oedema progression. Endothelial barrier function was quantified by measuring alveolar-capillary permeability to a fluorescently labeled inulin, a large polysaccharide molecule. Inulin was introduced into the lower chamber together with interleukin-2 (IL-2), one of the major cytokines.

Figure 2. The two-chamber organ-on-a-chip device, with epithelial and endothelial cell layers separated by a membrane, and a mechanical vacuum-strain mechanism. Figure 2. The chip chamber used in the ‘organ-on-a-chip’ device: epithelial cells over endothelial cells, separated by a porous membrane, with vacuum channels applying cyclic mechanical strain.

Images next to the graph below illustrate immunostaining patterns for junctional proteins — epithelial occludin (green) and endothelial VE-cadherin (red) — in control conditions and after exposure to cyclic mechanical strain (10% at 0.2 Hz) along with IL-2 for 3 days. White arrows indicate intercellular gaps.

Figure 3. Barrier permeability over time for four conditions, plus immunostaining images for occludin and VE-cadherin under control vs IL-2 + strain conditions. Figure 3. Barrier permeability (a.u.) vs. time (hours) for four conditions: IL-2 + 10% strain (highest), IL-2 no strain, 10% strain alone, and control (both near baseline). Right: immunostaining for occludin (Epi, green) and VE-cadherin (Endo, red) — control vs. IL-2 + strain, with white arrows marking intercellular gaps.

Based on the data provided, indicate whether the following statements are true or false:

A. The most likely consequence of increased barrier permeability in vivo is increased blood oxygen saturation.

B. Occludin staining works as a secondary marker to show increased gaps between endothelial cells and as such must be nearly identical to the VE-cadherin staining.

C. Cyclic stretch was used to simulate repetitive breathing patterns and not to mimic repetitive arterial pressure pulsations.

D. Under conditions of cyclic stretch and the presence of IL-2, the addition of albumin into culture media should not affect the volume of fluid leaving the lower chamber reflecting the oedema model.

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Question reproduced from IBO 2022, Theoretical Paper 1, licensed under CC BY-NC-SA 4.0 — attributed to the International Biology Olympiad. Open the full exam PDF · Community solutions (unofficial)