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

Table 2 Comparison of characteristics among lung organoids derived from different stem cell sources

	ASCs	iPSCs	ESCs
Main sources	Autologous lung tissue from patients (AT2 cells, airway basal cells, etc.)	Somatic cell reprogramming (e.g., from fibroblasts, peripheral blood mononuclear cells, etc.)	Inner cell mass of blastocysts (allogeneic)
Applicable to pulmonary disease scenarios	Airway epithelial reconstruction; local tissue repair	Modeling of developmental disorders; autologous transplantation following gene correction	Modeling of early lung development (e.g., congenital anomalies); investigation of key signaling pathways (FGF, Wnt)
Cost	Due to limitations in biopsy tissue accessibility and amplification capacity, the cost of personalized sample acquisition is high	Reprogramming and directed differentiation techniques are complex, with high costs associated with reagents and quality control materials	High, associated with acquisition, specialized maintenance, and ethical compliance procedures
Advantage	Short cultivation cycle, high maturity; preserves tissue specificity and epigenetic characteristics	Nearly unlimited amplification capacity; multi-lineage differentiation potential	Nearly unlimited amplification capacity; multi-lineage differentiation potential; serves as a vital tool for early-stage lung development research
Limitations	Cannot differentiate into non-epithelial lineages; may harbor disease-associated genetic alterations	Reprogramming carries a tumorigenic risk; there are significant inter-batch variations in cell maturity	Ethical constraints; immune rejection risk in allogeneic settings; teratoma formation potential
Focus of organoid validation	Assessment of local epithelial regenerative potential; functional validation prior to autologous transplantation	Differentiation efficiency and maturity monitoring; long-term genomic stability tracking	Monitoring of differentiation efficiency and maturity; evaluation of teratoma risk; basic developmental research

The comparative assessment in this table is a qualitative synthesis of published literature and expert interpretation, rather than a validated consensus ranking or meta-analysis conclusion. ASC: Adult stem cell; iPSC: Induced pluripotent stem cell; ESC: Embryonic stem cell; AT2: Alveolar type 2; FGF: Fibroblast growth factor.