Radiation-induced Bystander Effects in Cultured Human Stem Cells

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2010 Dec 15

PMID 21152027

Citations 19

Authors

Mykyta V Sokolov

Ronald D Neumann

Affiliations

Soon will be listed here.

Abstract

Background: The radiation-induced "bystander effect" (RIBE) was shown to occur in a number of experimental systems both in vitro and in vivo as a result of exposure to ionizing radiation (IR). RIBE manifests itself by intercellular communication from irradiated cells to non-irradiated cells which may cause DNA damage and eventual death in these bystander cells. It is known that human stem cells (hSC) are ultimately involved in numerous crucial biological processes such as embryologic development; maintenance of normal homeostasis; aging; and aging-related pathologies such as cancerogenesis and other diseases. However, very little is known about radiation-induced bystander effect in hSC. To mechanistically interrogate RIBE responses and to gain novel insights into RIBE specifically in hSC compartment, both medium transfer and cell co-culture bystander protocols were employed.

Methodology/principal Findings: Human bone-marrow mesenchymal stem cells (hMSC) and embryonic stem cells (hESC) were irradiated with doses 0.2 Gy, 2 Gy and 10 Gy of X-rays, allowed to recover either for 1 hr or 24 hr. Then conditioned medium was collected and transferred to non-irradiated hSC for time course studies. In addition, irradiated hMSC were labeled with a vital CMRA dye and co-cultured with non-irradiated bystander hMSC. The medium transfer data showed no evidence for RIBE either in hMSC and hESC by the criteria of induction of DNA damage and for apoptotic cell death compared to non-irradiated cells (p>0.05). A lack of robust RIBE was also demonstrated in hMSC co-cultured with irradiated cells (p>0.05).

Conclusions/significance: These data indicate that hSC might not be susceptible to damaging effects of RIBE signaling compared to differentiated adult human somatic cells as shown previously. This finding could have profound implications in a field of radiation biology/oncology, in evaluating radiation risk of IR exposures, and for the safety and efficacy of hSC regenerative-based therapies.

Citing Articles

Proteins Marking the Sequence of Genotoxic Signaling from Irradiated Mesenchymal Stromal Cells to CD34+ Cells.

Kohl V, Drews O, Costina V, Bierbaum M, Jawhar A, Roehl H Int J Mol Sci. 2021; 22(11).

PMID: 34072546 PMC: 8197937. DOI: 10.3390/ijms22115844.

Radiation Response of Murine Embryonic Stem Cells.

Hellweg C, Shinde V, Srinivasan S, Henry M, Rotshteyn T, Baumstark-Khan C Cells. 2020; 9(7).

PMID: 32660081 PMC: 7408589. DOI: 10.3390/cells9071650.

Mitochondrial adaptation in human mesenchymal stem cells following ionizing radiation.

Patten D, Ouellet M, Allan D, Germain M, Baird S, Harper M FASEB J. 2019; 33(8):9263-9278.

PMID: 31112400 PMC: 6662961. DOI: 10.1096/fj.201801483RR.

Changes in gene expression as one of the key mechanisms involved in radiation-induced bystander effect.

Sokolov M, Neumann R Biomed Rep. 2018; 9(2):99-111.

PMID: 30013775 PMC: 6036822. DOI: 10.3892/br.2018.1110.

Molecular mechanism of bystander effects and related abscopal/cohort effects in cancer therapy.

Wang R, Zhou T, Liu W, Zuo L Oncotarget. 2018; 9(26):18637-18647.

PMID: 29719632 PMC: 5915099. DOI: 10.18632/oncotarget.24746.

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