ArticleStem cells translational medicine2026
A human iPSC-derived 3D spinal cord organoid model to study radiation-induced neural injury.
Article in Stem cells translational medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundRadiation therapy remains a cornerstone in the treatment of primary and metastatic tumors; however, its efficacy is limited by the spinal cord's high sensitivity to radiation-induced injury. To better understand the mechanisms underlying spinal cord radiosensitivity, we developed a three-dimensional human spinal cord organoid model derived from human-induced pluripotent stem cells using a neuroectodermal differentiation protocol that closely mimics embryonic spinal cord development.
methodsMature spinal cord organoids were exposed to a clinically relevant 2 Gy dose of ionizing radiation, and subsequent assessments included evaluation of DNA damage, astrocytic response, and neuronal functionality.
resultsThe organoids successfully recapitulated key features of spinal cord development, including neural differentiation, spontaneous electrophysiological activity, and functional maturation. Radiation exposure led to pronounced DNA double-strand breaks, particularly in SOX2-expressing progenitor cells. Astrocyte hyperplasia was evident through increased GFAP expression, indicating a reactive gliosis response. Electrophysiological analysis revealed a marked reduction in spike frequency and burst activity, indicative of impaired neuronal function. Although partial recovery was observed over time, functional deficits persisted, suggesting sustained damage.
conclusionThis human spinal cord organoid model offers a physiologically relevant platform for studying radiation-induced spinal cord injury and provides valuable insights into the cellular and functional consequences of radiation exposure. It holds significant potential for advancing neuroprotective strategies and therapeutic interventions targeting radiation-induced damage in the central nervous system.
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