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Peer-reviewedCC BYPrecision clinical medicine

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

  • Sara Benedetti1
  • Hana Štupica2
  • Gian Vincenzo Zuccotti3,4
  • Volkmar Weissig5
  • Davide Marotta6,7
  • Carlo Pappone1,8,9
  • Alba Tull10
  • Kathleen H Rubins11
  • Afshin Beheshti12,13,14,15
  • Christopher E Mason12,16,17,18
  • Simona Ferraro3
18 affiliations
  1. 1Arrhythmia and Electrophysiology Centre, IRCCS Policlinico San Donato, San Donato Milanese, Milan 20097, Italy.
  2. 2Center for Neurogenomics and Cognitive Research, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The Netherlands.
  3. 3Department of Pediatrics, Buzzi Children's Hospital, Milan 20154, Italy.
  4. 4Department of Biomedical and Clinical Science, University of Milan, Milan 20157, Italy.
  5. 5Department of Pharmaceutical Science, Midwestern University College of Pharmacy Glendale, Arizona, AZ 85308, United States.
  6. 6Helogen Corporation, New York, NY 10013, United States.
  7. 7School of Biomedical Engineering, University of Technology Sydney, Sydney, NSW 2007, Australia.
  8. 8Department of Cardiology, Electrophysiology, and Cardiac Pacing Unit, Vita-Salute San Raffaele University, Milan 20132, Italy.
  9. 9Institute for Molecular and Translational Cardiology (IMTC), IRCCS Policlinico San Donato, San Donato Milanese, Milan 20097, Italy.
  10. 10Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA 15213, United States.
  11. 11National Aeronautics and Space Administration, Johnson Space Flight Center, Houston, TX 77058, United States.
  12. 12Center for Space Biomedicine, Trivedi Institute for Space and Global Biomedicine, University of Pittsburgh, Pittsburgh, PA 15219, United States.
  13. 13Department of Computational and Systems Biology, University of Pittsburgh, Pittsburgh, PA 15219, United States.
  14. 14Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, United Sttes.
  15. 15McGowan Institute for Regenerative Medicine, Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15219, United States.
  16. 16The HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, Weill Cornell Medicine, New York, NY 10021, United States.
  17. 17The WorldQuant Initiative for Quantitative Prediction, Weill Cornell Medicine, New York, NY 10065, United States.
  18. 18Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY 10065, United States.
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Abstract

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.

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Cite

BibTeXRIS
BibTeX
@article{benedetti2026human,
  title = {{Human induced pluripotent stem cells and organoid models in space for investigating severe pediatric metabolic and congenital disorders.}},
  author = {Sara Benedetti and Hana Štupica and Gian Vincenzo Zuccotti and Volkmar Weissig and Davide Marotta and Carlo Pappone and Alba Tull and Kathleen H Rubins and Afshin Beheshti and Christopher E Mason and Simona Ferraro},
  journal = {Precision clinical medicine},
  year = {2026},
  month = sep,
  doi = {10.1093/pcmedi/pbag028},
  url = {https://europepmc.org/article/MED/42910274},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Human induced pluripotent stem cells and organoid models in space for investigating severe pediatric metabolic and congenital disorders.
AU  - Sara Benedetti
AU  - Hana Štupica
AU  - Gian Vincenzo Zuccotti
AU  - Volkmar Weissig
AU  - Davide Marotta
AU  - Carlo Pappone
AU  - Alba Tull
AU  - Kathleen H Rubins
AU  - Afshin Beheshti
AU  - Christopher E Mason
AU  - Simona Ferraro
PY  - 2026
DA  - 2026/09/29
JO  - Precision clinical medicine
DO  - 10.1093/pcmedi/pbag028
UR  - https://europepmc.org/article/MED/42910274
AB  - 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.
SN  - 2096-5303
SN  - 2516-1571
ER  -