PhD Scientific Days 2024

Budapest, 9-10 July 2024

Pathological and Oncological Sciences II.

Bone Marrow-Derived Extracellular Vesicles from Irradiated Mice Are Able To Induce Senescence in Distinct Subpopulations of the Stem Cell Compartment and the Hematopoietic Microenvironment

Author(s)

Martina Forgács1, Katalin Balázs1, Ilona Barbara Csordás1, Eszter Szarka1, Balázs Gyebrovszki1, Katalin Lumniczky1
1: National Centre for Public Health and Pharmacy, Department of Radiobiology and Radiohygiene, Unit of Radiation Medicine, Budapest, Hungary

Text of the abstract

Introduction: Bone marrow (BM) stroma is a special microenvironment which has a strong influence on the function of the stem cell compartment. Radiation exposure can induce cellular senescence in specific cell types via dysregulation of specific molecular pathways. Previous studies (Kis et al, 2022) demonstrated that extracellular vesicles (EVs) from irradiated mice influence the cellular composition of the BM in the acute phase after irradiation.

Aims: The aim of this project is to better understand radiation-induced alterations and the role of the EVs released by the irradiated cells, by a long-term follow-up of phenotypical changes and senescence development in specific BM and stromal cell subpopulations.

Method: Male CBA/Ca mice were (I) directly irradiated with either 0Gy (controls) or 3Gy X-rays; or (II) injected with BM-derived EVs isolated from directly irradiated animals; or (III) both irradiated and injected with EVs. Long bones were isolated 3, 6 and 9 months after treatment. Single cell suspensions were prepared separately from the BM and bone. Major cell subpopulations within the bone and BM and B-gal staining indicative of cellular senescence in the respective cell subpopulations were investigated by flow cytometry.

Results: Ionizing radiation induced high level of cellular senescence in specific BM and stromal cell subpopulations, especially in those localized in the stromal environment. As a result of EV treatment the level of the cellular senescence in the mesenchymal stem cells and endothelial cells decreased in the BM and increased in the stroma during the follow-up, while in the case of fibroblast decreased the level of cellular senescence in the two system.

Conclusion: In conclusion, we showed that, not only ionizing radiation can cause abnormalities and trigger senescence in specific BM and stromal cell types, but also BM-derived EVs isolated from directly irradiated animals can induce bystander effect in certain stromal subpopulations in the recipient mice for a long-term period.

Reference: Kis, D., et al. Extracellular Vesicles Derived from Bone Marrow in an Early Stage of Ionizing Radiation Damage Are Able to Induce Bystander Responses in the Bone Marrow. Cells 2022, 11, 155. https://doi.org/10.3390/ cells11010155