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KMID : 1148920120460020081
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Nuclear Medicine and Molecular Imaging
2012 Volume.46 No. 2 p.81 ~ p.88
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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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Park Bok-Nam
Shim Woo-Young
Ahn Young-Hwan
Lee Jae-Ho
An Young-Sil
Yoon Joon-Kee
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Abstract
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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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KEYWORD
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111In-tropolone, Mesenchymal stem cells, Cell cycle, Apoptosis, Necrosis
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