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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.<\/jats:p>\n                  <jats:p>Methods: Mature spinal cord organoids were exposed to a clinically relevant 2\u2009Gy dose of ionizing radiation, and subsequent assessments included evaluation of DNA damage, astrocytic response, and neuronal functionality.<\/jats:p>\n                  <jats:p>Results: The 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.<\/jats:p>\n                  <jats:p>Conclusion: This 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.<\/jats:p>","DOI":"10.1093\/stcltm\/szag042","type":"journal-article","created":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T11:41:14Z","timestamp":1775821274000},"source":"Crossref","is-referenced-by-count":0,"title":["A human iPSC-derived 3D spinal cord organoid model to study radiation-induced neural injury"],"prefix":"10.1093","volume":"15","author":[{"given":"Yifei","family":"Jiang","sequence":"first","affiliation":[{"name":"Department of Microsurgery, Orthopedic Trauma and Hand Surgery, The First Affiliated Hospital, Sun Yat-sen University , Guangzhou, 510080,","place":["China"]},{"name":"Guangdong Province Engineering Laboratory for Soft Tissue Biofabrication, Sun Yat-sen University , Guangzhou, 510080,","place":["China"]},{"name":"Guangdong Provincial Peripheral Nerve Tissue Engineering and Technology 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