Pharma Focus Asia

Effects of Acute Low-moderate Dose Ionizing Radiation to Human Brain Organoids

Foluwasomi A. Oyefeso, Gabriela Goldberg, Nana Yaa P. S. Opoku, Marcelo Vazquez, Antonella Bertucci, Zhong Chen, Charles Wang, Alysson R. Muotri, Michael J. Pecaut.

Abstract

Human exposure to low-to-moderate dose ionizing radiation (LMD-IR) is increasing via environmental, medical, occupational sources. Acute exposure to LMD-IR can cause subclinical damage to cells, resulting in altered gene expression and cellular function within the human brain. It has been difficult to identify diagnostic and predictive biomarkers of exposure using traditional research models due to factors including lack of 3D structure in monolayer cell cultures, limited ability of animal models to accurately predict human responses, and technical limitations of studying functional human brain tissue.

Introduction

The risks of radiation exposure can be divided into three categories: acute (occurring within the first few days after exposure), early delayed (occurring within a few weeks or months after exposure), and late delayed (occurring within several months or years after exposure). Acute radiation syndrome (ARS) describes the pathological changes that occur within days or weeks after exposure to ionizing radiation (IR).

Materials and Methods:

Human induced pluripotent stem cell (hiPSC) culture

Two distinct hiPSC lines (WT83 C6 & XB C2) were used to generate organoids in this study (S2 Table). The methods used to generate and characterize these lines have been described previously.

Generation of 3-D brain organoids

To generate brain organoids, hiPSC cultures were dissociated into a single cell suspension using Accutase (Innovative Cell Technologies, Inc.

Discussion:

Due to the increasing likelihood of exposure to low doses of ionizing radiation (IR) in clinical and occupational settings, it is becoming increasingly important to characterize the radiosensitivity of different cell types, particularly the subclinical responses of human brain tissue. The National Academies of Sciences, Engineering, and Medicine recently released a report highlighting the urgency of making advances in radiobiological research, which brought up an urgent need to use brain organoids in IR research.

Acknowledgments:

We are very grateful to Tami Jones and Dr. Seta Stanbouly for project supervision and providing materials that contributed to the progress of this research. We thank Dr. Gregory Nelson, and Dr Xiao Mao, and Dr. Chris Wilson for key expertise that helped to guide the development of this research. We thank Dr. Xiaobing Zhang for providing hiPSCs used to generate organoids in this study.

Citation: Oyefeso FA, Goldberg G, Opoku NYPS, Vazquez M, Bertucci A, Chen Z, et al. (2023) Effects of acute low-moderate dose ionizing radiation to human brain organoids. PLoS ONE 18(5): e0282958. https://doi.org/10.1371/journal.pone.0282958

Editor: Jyotshna Kanungo, National Center for Toxicological Research, UNITED STATES

Received: June 7, 2022; Accepted: February 27, 2023; Published: May 31, 2023.

Copyright: © 2023 Oyefeso et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: All relevant data are within the paper and its Supporting information files.

Funding: M.J.P. received support in part through National Institutes of Health grant U19AI067773, National Aeronautics and Space Administration Research Grant NNX13AN34G, and NSF/CASIS grant 2126309. F.O. received support through the LLU Initiative for Maximizing Student Development under National Institutes of General Medical Sciences grant R25 GM060507. A.R.M. received National Science Foundation / Center for the Advancement of Science in Space grant 2126309. Imaging and analysis was performed in the LLUSM Advanced Imaging and Microscopy Core that is supported by National Science Foundation grant MRI-DBI 0923559. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.


Competing interests: A.R.M. is a co-founder and has equity interest in TISMOO, a company dedicated to genetic analysis and human brain organogenesis, focusing on therapeutic applications customized for autism spectrum disorders and other neurological disorders origin genetics. The terms of this arrangement have been reviewed and approved. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

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