Human induced pluripotent stem cells and organoid models in space for investigating severe pediatric metabolic and congenital disorders.

As biomedical research in space expands, microgravity and spaceflight-associated stressors are revealing cellular responses that may provide new insights into rare and severe metabolic and congenital disorders. Human induced pluripotent stem cells (hiPSCs) and organoids are particularly promising as they enable patient-specific modelling in the space environment. In this review, we examine the current literature on space-based hiPSC experimental models, highlighting their relevance to pediatric disorders with well-defined genetic backgrounds, namely mitochondrial diseases and congenital heart disorders. We summarize the evidence that spaceflight conditions alter mitochondrial function, cytoskeletal organization, oxidative stress, calcium handling, cellular maturation, and gene expression, and discuss how these responses may converge with metabolic disease-associated phenotypes. We highlight both adaptive and pathological responses reported in space-based hiPSC studies and identify key experimental and mechanistic gaps. Finally, we consider how advances in stem cell technologies and space-based biomedical research may enable the development of personalized, patient-specific disease models and therapeutics for rare pediatric diseases, ultimately accelerating translational discovery and clinical innovation.