Lung organoids for preclinical evaluation of stem cell therapies: Opportunities, evidence, and translational challenges

Table 4 Comparison of the advantages and limitations among lung organoids, lung-on-a-chip systems, animal models, and two-dimensional cell cultures

Comparison dimensions	Animal model	2D cell culture	Lung organoids	Lung-on-a-chip
Human-derived physiological fidelity	Moderate	Low	High	Medium to high
Cost	Low	Low	Medium to high	Moderate
Throughput	Low	High	High	Moderate
Level of operational difficulty	Medium to high	Low	Low	Low
Reproducibility and standardization	Moderate	High	Moderate	Moderate
Applicability of stem cell therapy	Moderate	Low	High	High
Core limitations	Significant species differences; ethical controversies	Lack of a physiological gradient; absence of multicellular interactions or an immune microenvironment	No physiological mechanical stress; lacks functional vascular and nervous systems	High technical complexity; incomplete vascularization
Classic applications	Research on systemic disease mechanisms; in vivo analysis; systemic toxicity assessment	Early drug screening; basic research on cellular signaling pathways; large-scale cytotoxicity testing	Disease modeling; PDO drug sensitivity testing; research on stem cell differentiation and repair mechanisms; establishment of a precision medicine biobank	The relationship between mechanics and disease; organ-organ interactions; assessment of inhaled nanoparticle toxicity

The comparative assessment results presented in this table reflect the authors’ qualitative synthesis of existing literature and expert interpretations, rather than representing a validated consensus ranking or the conclusions of a meta-analysis. The ratings (‘Low’, ‘Moderate’, ‘High’) are descriptive generalizations based on the volume and directness of available evidence for each platform and should be interpreted as relative indicators rather than absolute performance metrics. These ratings may vary depending on specific experimental contexts, disease models, and research questions. They should be regarded as indicative references, not as quantitative benchmarks. PDO: Patient-derived organoid.