Work

A human iPSC-derived 3D spinal cord organoid model to study radiation-induced neural injury

Year: 2026

Type: article

Abstract: BACKGROUND: Radiation 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. METHODS: Mature 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. 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. 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.

Source: Stem Cells Translational Medicine

DOI: 10.1093/stcltm/szag042