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

Table 1 The lung organoid platform as feasibility evidence for preclinical stem cell validation

Assessment dimension	Study type	Key findings	Evidence level	Limitations	Ref.
Immunomodulatory mechanism	Murine lung organoid-macrophage co-culture	Bone marrow-derived MSCs suppressed LPS-induced proinflammatory cytokines and NF-κB activation in alveolar and interstitial macrophages	Direct (murine organoid)	Not validated in human organoids; culture medium incompatibility limits generalizability	[18]
Long-term safety monitoring (tumorigenicity, genetic stability)	Theoretical framework	Genomic approaches (WGS, karyotyping, scRNA-seq) proposed for assessing oncogenic risk of candidate cells	Theoretical (proof-of-principle)	No prospective study	[65,81,82]

Evidence level definitions: Direct evidence - stem cell or extracellular vesicle therapies directly validated within a specified organotypic system; theoretical evidence - proposed applications for which no directly validated studies have been conducted. MSCs: Mesenchymal stromal cells; LPS: Lipopolysaccharide; NF-κB: Nuclear factor kappa B; WGS: Whole genome sequencing; scRNA-seq: Single-cell RNA sequencing.