Nucl Med Mol Imaging.  2012 Jun;46(2):81-88.

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

• Park BN
• Shim W
• Ahn YH
• Lee JH
• An YS
• Yoon JK

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.

Keyword

111In-tropolone; Mesenchymal stem cells; Cell cycle; Apoptosis; Necrosis

MeSH Terms

Animals
Apoptosis
Bone Marrow
Cell Aging
Cell Cycle
Cell Cycle Checkpoints
Cell Death
Flow Cytometry
G1 Phase Cell Cycle Checkpoints
Humans
Light
Mesenchymal Stromal Cells
Necrosis
Propidium
Rats
Propidium