Journal Article

DKFZ-2021-03243

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Assessment of Normal Tissue Radiosensitivity by Evaluating DNA Damage and Repair Kinetics in Human Brain Organoids.

Bojcevski, J. (First author)DKFZ* ; Wang, C.DKFZ* ; Liu, H.DKFZ* ; Abdollahi, A.DKFZ* ; Dokic, I. (Last author)DKFZ*

2021
Molecular Diversity Preservation International Basel

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Please use a persistent id in citations: doi:10.3390/ijms222413195

Abstract: DNA-double strand break (DSB), detected by immunostaining of key proteins orchestrating repair, like γH2AX and 53BP1, is well established as a surrogate for tissue radiosensitivity. We hypothesized that the generation of normal brain 3D organoids ('mini-brains') from human induced pluripotent stem cells (hiPSC) combined with detection of DNA damage repair (DDR) may hold the promise towards developing personalized models for the determination of normal tissue radiosensitivity. In this study, cerebral organoids, an in vitro model that stands in its complexity between 2D cellular system and an organ, have been used. To quantify radiation-induced response, immunofluorescent staining with γH2AX and 53BP1 were applied at early (30 min, initial damage), and late time points (18 and 72 h, residual damage), following clinical standard 2 Gy irradiation. Based on our findings, assessment of DDR kinetics as a surrogate for radiosensitivity in hiPSC derived cerebral organoids is feasible. Further development of mini-brains recapitulating mature adult neuronal tissue and implementation of additional signaling and toxicity surrogates may pave the way towards development of next-generation personalized assessment of radiosensitivity in healthy neuronal tissue.

Keyword(s): DNA damage repair ; brain organoids ; mini-brains ; neurotoxicity ; radiation ; radiosensitivity

Note: #EA:E210#LA:E210#

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Contributing Institute(s):

1. E210 Translationale Radioonkologie (E210)
2. DKTK HD zentral (HD01)
3. A240 Molekulare Neurogenetik (A240)

Research Program(s):

1. 315 - Bildgebung und Radioonkologie (POF4-315) (POF4-315)

Appears in the scientific report 2021

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