{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T02:34:17Z","timestamp":1760150057800,"version":"build-2065373602"},"reference-count":49,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2023,10,10]],"date-time":"2023-10-10T00:00:00Z","timestamp":1696896000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University of Cincinnati Cancer Center, College of Medicine"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Radiation therapy (RT) is a crucial treatment modality for central nervous system (CNS) tumors but toxicity to healthy CNS tissues remains a challenge. Additionally, environmental exposure to radiation during nuclear catastrophes or space travel presents a risk of CNS toxicity. However, the underlying mechanisms of radiation-induced CNS toxicity are not fully understood. Neural progenitor cells (NPCs) are highly radiosensitive, resulting in decreased neurogenesis in the hippocampus. This study aimed to characterize a novel platform utilizing rat NPCs cultured as 3D neurospheres (NSps) to screen the safety and efficacy of experimental drugs with and without radiation exposure. The effect of radiation on NSp growth and differentiation was assessed by measuring sphere volume and the expression of neuronal differentiation markers Nestin and GFAP and proliferation marker Ki67. Radiation exposure inhibited NSp growth, decreased proliferation, and increased GFAP expression, indicating astrocytic differentiation. RNA sequencing analysis supported these findings, showing upregulation of Notch, BMP2\/4, S100b, and GFAP gene expression during astrogenesis. By recapitulating radiation-induced toxicity and astrocytic differentiation, this single-NSp culture system provides a high-throughput preclinical model for assessing the effects of various radiation modalities and evaluates the safety and efficacy of potential therapeutic interventions in combination with radiation.<\/jats:p>","DOI":"10.3390\/cancers15204916","type":"journal-article","created":{"date-parts":[[2023,10,10]],"date-time":"2023-10-10T06:14:04Z","timestamp":1696918444000},"page":"4916","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Development of a Single-Neurosphere Culture to Assess Radiation Toxicity and Pre-Clinical Cancer Combination Therapy Safety"],"prefix":"10.3390","volume":"15","author":[{"given":"Bedika","family":"Pathak","sequence":"first","affiliation":[{"name":"Center for Fetal and Placental Research, Cincinnati Children\u2019s Hospital Medical Center (CCHMC), Cincinnati, OH 45229, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Taylor E.","family":"Lange","sequence":"additional","affiliation":[{"name":"Department of Cancer Biology, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA"},{"name":"Division of Oncology, Cancer and Blood Diseases Institute, Cincinnati Children\u2019s Hospital Medical Center (CCHMC), Cincinnati, OH 45229, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristin","family":"Lampe","sequence":"additional","affiliation":[{"name":"Center for Fetal and Placental Research, Cincinnati Children\u2019s Hospital Medical Center (CCHMC), Cincinnati, OH 45229, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ella","family":"Hollander","sequence":"additional","affiliation":[{"name":"Center for Fetal and Placental Research, Cincinnati Children\u2019s Hospital Medical Center (CCHMC), Cincinnati, OH 45229, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marina","family":"Oria","sequence":"additional","affiliation":[{"name":"Center for Fetal and Placental Research, Cincinnati Children\u2019s Hospital Medical Center (CCHMC), Cincinnati, OH 45229, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kendall P.","family":"Murphy","sequence":"additional","affiliation":[{"name":"Center for Fetal and Placental Research, Cincinnati Children\u2019s Hospital Medical Center (CCHMC), Cincinnati, OH 45229, USA"},{"name":"Department of Orthopedic Surgery, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nathan","family":"Salomonis","sequence":"additional","affiliation":[{"name":"Division of Biomedical Informatics, Cincinnati Children\u2019s Hospital Medical Center (CCHMC), Cincinnati, OH 45229, USA"},{"name":"Departments of Pediatrics and Bioinformatics, University of Cincinnati, Cincinnati, OH 45221, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9395-2718","authenticated-orcid":false,"given":"Mathieu","family":"Sertorio","sequence":"additional","affiliation":[{"name":"University of Cincinnati Cancer Center, Cincinnati, OH 45267, USA"},{"name":"Department of Radiation Oncology, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9132-9271","authenticated-orcid":false,"given":"Marc","family":"Oria","sequence":"additional","affiliation":[{"name":"University of Cincinnati Cancer Center, Cincinnati, OH 45267, USA"},{"name":"Department of Radiation Oncology, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA"},{"name":"University of Cincinnati Brain Tumor Center, Cincinnati, OH 45219, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,10,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Alessi, I., Caroleo, A.M., de Palma, L., Mastronuzzi, A., Pro, S., Colafati, G.S., Boni, A., Della Vecchia, N., Velardi, M., and Evangelisti, M. 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