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High-Dose 111In Induces G1 Cell Cycle Arrest and Cell Death in Rat Bone Marrow Mesenchymal Stem Cells

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Abstract

Purpose

This study was performed to evaluate the effect of 111In-labeling on the cell growth, cycle and viability of bone marrow mesenchymal stem cells (BMSCs).

Methods

Rat BMSCs were labeled with various doses of 111In (0.4–11.1 Bq/cell). The growth curve of 111In-BMSCs was obtained up to 14th day of labeling. The cell cycle was evaluated by 5-bromo-2-deoxyuridine (BrdU) labeling or propidium iodide (PI) staining. Senescent cells were counted under a light microscope after staining with 5-bromo-4-chloro-3-indolyl-D-galactopyranoside. Flow cytometry was performed to measure apoptotic and necrotic fractions after staining with annexin V-FITC and PI.

Results

The growth of BMSCs labeled with higher doses of 111In (4.4 or 11.1 Bq/cell) was significantly inhibited from the 3rd day of labeling. Flow cytometry revealed less BrdU-positive BMSCs at 11.1 Bq 111In/cell during all measurement days and G1 arrest at 4.4 and 11.1 Bq 111In/cell. Significant increases in apoptosis and necrosis were also observed at 4.4 (3.04%/1.35%) and 11.1 Bq 111In/cell (9.07%/3.18%) on the 14th day (control = 1.60%/0.39%). However, no cellular senescence was visualized up to the 14th day.

Conclusion

A high dose of 111In-labeling induced cell cycle arrest and death in BMSCs; therefore, it should be used with a careful dosimetry in case of applying it to humans.

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Acknowledgements

This work was supported by a Korea Research Foundation Grant funded by the Korean Government (MOEHRD, Basic Research Promotion Fund) (KRF-2008-313-E00446) and by 2008 grant from Department of Medical Sciences, The Graduate School, Ajou University (Yoon J.K.).

Conflicts of Interest

None.

Author information

Authors and Affiliations

  1. Department of Nuclear Medicine and Molecular Imaging, Ajou University School of Medicine, Suwon, 442-749, Republic of Korea

    Bok-Nam Park, Young-Sil An & Joon-Kee Yoon

  2. Institute for Neuroregeneration and Stem Cell Research, Ajou University School of Medicine, Suwon, Republic of Korea

    Wooyoung Shim & Young Hwan Ahn

  3. Department of Molecular Science and Technology, Ajou University, Suwon, Republic of Korea

    Wooyoung Shim

  4. Department of Neurosurgery, Ajou University School of Medicine, Suwon, Republic of Korea

    Young Hwan Ahn

  5. Department of Biochemistry, Ajou University School of Medicine, Suwon, Republic of Korea

    Jae-Ho Lee

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  1. Bok-Nam Park
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  2. Wooyoung Shim
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  4. Jae-Ho Lee
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  5. Young-Sil An
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Correspondence to Joon-Kee Yoon.

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Park, BN., Shim, W., Ahn, Y.H. et al. High-Dose 111In Induces G1 Cell Cycle Arrest and Cell Death in Rat Bone Marrow Mesenchymal Stem Cells. Nucl Med Mol Imaging 46, 81–88 (2012). https://doi.org/10.1007/s13139-011-0124-6

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  • DOI: https://doi.org/10.1007/s13139-011-0124-6

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