The effect of ionising radiation on the phenotype of bone marrow-derived extracellular vesicles

Kis, Dávid; Persa, Eszter; Szatmári, Tünde; Antal, Lilla; Bóta, Attila; Csordás, Ilona Barbara; Hargitai, Rita; Jezsó, Bálint; Kis, Enikő; Mihály, Judith; Sáfrány, Géza; Varga, Zoltán; Lumniczky, Katalin

doi:10.1259/bjr.20200319

Cited by 11 publications

(8 citation statements)

References 41 publications

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“…It has been shown that whole body irradiation influences the secretion of EVs from bone marrow cell subpopulations in mice: EVs containing mesenchymal stem cell markers CD29 and CD44 decreased, while EVs with haematopoietic stem cell or lymphoid progenitor markers increased after irradiation (Kis et al 2020 ). Several studies suggest increased EV release after irradiation in in vitro and in vivo models.…”

Section: Out-of-field Effects: Model Systems and Mechanismsmentioning

confidence: 99%

Out-of-field effects: lessons learned from partial body exposure

Pazzaglia

Eidemüller

Lumniczky³

et al. 2022

Radiat Environ Biophys

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Partial body exposure and inhomogeneous dose delivery are features of the majority of medical and occupational exposure situations. However, mounting evidence indicates that the effects of partial body exposure are not limited to the irradiated area but also have systemic effects that are propagated outside the irradiated field. It was the aim of the “Partial body exposure” session within the MELODI workshop 2020 to discuss recent developments and insights into this field by covering clinical, epidemiological, dosimetric as well as mechanistic aspects. Especially the impact of out-of-field effects on dysfunctions of immune cells, cardiovascular diseases and effects on the brain were debated. The presentations at the workshop acknowledged the relevance of out-of-field effects as components of the cellular and organismal radiation response. Furthermore, their importance for the understanding of radiation-induced pathologies, for the discovery of early disease biomarkers and for the identification of high-risk organs after inhomogeneous exposure was emphasized. With the rapid advancement of clinical treatment modalities, including new dose rates and distributions a better understanding of individual health risk is urgently needed. To achieve this, a deeper mechanistic understanding of out-of-field effects in close connection to improved modelling was suggested as priorities for future research. This will support the amelioration of risk models and the personalization of risk assessments for cancer and non-cancer effects after partial body irradiation.

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Section: Out-of-field Effects: Model Systems and Mechanismsmentioning

confidence: 99%

Out-of-field effects: lessons learned from partial body exposure

Pazzaglia

Eidemüller

Lumniczky³

et al. 2022

Radiat Environ Biophys

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“…We also demonstrate the utility of urinary EVs as an effective source of biomarkers for detecting IR exposure. Previous reports have studied whole urine, whole plasma, and plasma EVs as sources for biomarkers of IR exposure and IR damage (3,11,(28)(29)(30)(31). Dyslipidemia has previously been observed after radiation exposure (3,12,(32)(33)(34)(35).…”

Section: Discussionmentioning

confidence: 99%

An optimized method for the isolation of urinary extracellular vesicles for molecular phenotyping: detection of biomarkers for radiation exposure

Hinzman

Jayatilake

Bansal

et al. 2022

Preprint

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Background: Urinary extracellular vesicles (EVs) are a source of biomarkers with broad potential applications across clinical research, including monitoring radiation exposure. A key limitation to their implementation is minimal standardization in EV isolation and analytical analysis methods. Further, most urinary EV isolation protocols necessitate large volumes of sample. This study aimed to compare and optimize isolation and analytical methods for EVs from small volumes of urine.Methods: 3 EV isolation methods were compared: ultracentrifugation, magnetic bead-based, and size-exclusion chromatography from 0.5 mL or 1 mL of rat and human urine. EV yield and mass spectrometry signals (Q-ToF and Triple Quad) were evaluated from each method. Metabolomic profiling was performed on EVs isolated from the urine of rats exposed to ionizing radiation 1-, 14-, 30- or 90-days post-exposure, and human urine from patients receiving thoracic radiotherapy for the treatment of lung cancer pre- and post-treatment.Results: Size-exclusion chromatography is the preferred method for EV isolation from 0.5 mL of urine. Mass spectrometry-based metabolomic analyses of EV cargo identified biochemical changes induced by radiation, including altered nucleotide, folate, and lipid metabolism. We have provided standard operating procedures for implementation of these methods in other laboratories.Conclusions: We demonstrate that EVs can be isolated from small volumes of urine and analytically investigated for their biochemical contents to detect radiation induced metabolomic changes. These findings lay a groundwork to develop future methods to monitor response to radiotherapy and can be extended to an array of molecular phenotyping studies aimed at characterizing EV cargo.

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“…For transmission electron microscopy (TEM) analysis, EVs were processed as described in [ 31 ]; namely, samples were applied to formvar-coated nickel grids and stained with 2% uranyl acetate ( v / v ) solution for 5 min. Grids were air-dried and viewed using a JEOL TEM 1011 TEM (JEOL, Peabody, MA, USA) operated at 80 kV.…”

Section: Methodsmentioning

confidence: 99%

Extracellular Vesicles Derived from Bone Marrow in an Early Stage of Ionizing Radiation Damage Are Able to Induce Bystander Responses in the Bone Marrow

Kis

Csordás²,

Persa³

et al. 2022

Cells

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Ionizing radiation (IR)-induced bystander effects contribute to biological responses to radiation, and extracellular vesicles (EVs) play important roles in mediating these effects. In this study we investigated the role of bone marrow (BM)-derived EVs in the bystander transfer of radiation damage. Mice were irradiated with 0.1Gy, 0.25Gy and 2Gy, EVs were extracted from the BM supernatant 24 h or 3 months after irradiation and injected into bystander mice. Acute effects on directly irradiated or EV-treated mice were investigated after 4 and 24 h, while late effects were investigated 3 months after treatment. The acute effects of EVs on the hematopoietic stem and progenitor cell pools were similar to direct irradiation effects and persisted for up to 3 months, with the hematopoietic stem cells showing the strongest bystander responses. EVs isolated 3 months after irradiation elicited no bystander responses. The level of seven microRNAs (miR-33a-3p, miR-140-3p, miR-152-3p, miR-199a-5p, miR-200c-5p, miR-375-3p and miR-669o-5p) was altered in the EVs isolated 24 hour but not 3 months after irradiation. They regulated pathways highly relevant for the cellular response to IR, indicating their role in EV-mediated bystander responses. In conclusion, we showed that only EVs from an early stage of radiation damage could transmit IR-induced bystander effects.

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The effect of ionising radiation on the phenotype of bone marrow-derived extracellular vesicles

Cited by 11 publications

References 41 publications

Out-of-field effects: lessons learned from partial body exposure

Out-of-field effects: lessons learned from partial body exposure

An optimized method for the isolation of urinary extracellular vesicles for molecular phenotyping: detection of biomarkers for radiation exposure

Extracellular Vesicles Derived from Bone Marrow in an Early Stage of Ionizing Radiation Damage Are Able to Induce Bystander Responses in the Bone Marrow

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