Differential Effects of X-Rays and High-Energy 56Fe Ions on Human Mesenchymal Stem Cells

Kurpinski, Kyle; Jang, Deok-Jin; Bhattacharya, Sanchita; Rydberg, Bjorn; Chu, Julia; So, Joanna; Wyrobek, Andy; Li, Song; Wang, Daojing

doi:10.1016/j.ijrobp.2008.10.002

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Volume 73, Issue 3 , Pages 869-877, 1 March 2009

Differential Effects of X-Rays and High-Energy ⁵⁶Fe Ions on Human Mesenchymal Stem Cells

Kyle Kurpinski, Ph.D.
- Department of Bioengineering, University of California–Berkeley, Berkeley, CA
Deok-Jin Jang, Ph.D.
- Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA
Sanchita Bhattacharya, M.S.
- Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA
Bjorn Rydberg, Ph.D.
- Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA
Julia Chu, B.S.
- Department of Bioengineering, University of California–Berkeley, Berkeley, CA
Joanna So, B.S.
- Department of Bioengineering, University of California–Berkeley, Berkeley, CA
Andy Wyrobek, Ph.D.
- Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA
Song Li, Ph.D.
- Department of Bioengineering, University of California–Berkeley, Berkeley, CA
Daojing Wang, Ph.D.
- Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA
- Reprint requests to: Daojing Wang, Ph.D., Life Sciences Division, Lawrence Berkeley National Laboratory, 1 Cyclotron Road, MS 977-225A, Berkeley, CA 94720. Tel: (510) 486-6592; Fax: (510) 495-2535

Received 12 May 2008; received in revised form 29 August 2008; accepted 3 September 2008. published online 19 December 2008.

Purpose

Stem cells hold great potential for regenerative medicine, but they have also been implicated in cancer and aging. How different kinds of ionizing radiation affect stem cell biology remains unexplored. This study was designed to compare the biological effects of X-rays and of high–linear energy transfer (LET) ⁵⁶Fe ions on human mesenchymal stem cells (hMSC).

Methods and Materials

A multi-functional comparison was carried out to investigate the differential effects of X-rays and ⁵⁶Fe ions on hMSC. The end points included modulation of key markers such as p53, cell cycle progression, osteogenic differentiation, and pathway and networks through transcriptomic profiling and bioinformatics analysis.

Results

X-rays and ⁵⁶Fe ions differentially inhibited the cell cycle progression of hMSC in a p53-dependent manner without impairing their in vitro osteogenic differentiation process. Pathway and network analyses revealed that cytoskeleton and receptor signaling were uniquely enriched for low-dose (0.1 Gy) X-rays. In contrast, DNA/RNA metabolism and cell cycle regulation were enriched for high-dose (1 Gy) X-rays and ⁵⁶Fe ions, with more significant effects from ⁵⁶Fe ions. Specifically, DNA replication, DNA strand elongation, and DNA binding/transferase activity were perturbed more severely by 1 Gy ⁵⁶Fe ions than by 1 Gy X-rays, consistent with the significant G2/M arrest for the former while not for the latter.

Conclusions

⁵⁶Fe ions exert more significant effects on hMSC than X-rays. Since hMSC are the progenitors of osteoblasts in vivo, this study provides new mechanistic understandings of the relative health risks associated with low- and high-dose X-rays and high-LET space radiation.

Radioresponse, High-LET, Cell cycle, Osteogenic differentiation, Transcriptomics