Abstract

Background: This study investigates the effect of 111In-oxine incorporation on the viability of bone marrow stromal cells (BMSCs) in vitro, and the applicability of 111In-oxine labeling and single-photon emission computed tomography (SPECT) imaging of the BMSCs transplanted in rat model of cerebral infarct in vivo. Methods: Rat BMSCs were labeled with 111In-oxine (10 Bq/cell). Cellular retention of radioactivity, cell survival, and proliferation capacity were evaluated for 7 days. The rats were subjected to permanent middle cerebral artery occlusion. The 111In-oxine labeled BMSCs were stereotactically (1.0 х 1000000 cells) or intravenously (3.0 х 1000000 cells) transplanted at 7 days after the insult. Using SPECT, the behaviors of BMSCs were serially monitored during 14 days after transplantation. The distribution of engrafted cells was examined, using fluorescence immunohistochemistry. Results: Labeling efficiency was 35.8 ± 18.6 %, with 36.5 ± 20.6 % of 111In remaining in the BMSCs at 7 day. The radiolabeling did not affect cell viability, whereas proliferation capacity was significantly reduced. In vivo SPECT imaging clearly visualized that the transplanted BMSCs gradually migrated toward the peri-infarct area during 14 days after transplantation in the intracerebral group, but not in the intravenous group. The BMSCs were widely distributed in the peri-infarct area and some of them expressed neural cell markers in the intracerebral group, but not in the intravenous group. Conclusions: 111In-oxine labeling preserved viability of the BMSCs, while moderately impairing their proliferation capacity. SPECT imaging of 111In-oxine labeled BMSCs was valuable in monitoring the behaviors of donor cells into the rodent brain, and the results would also suggest that the intracerebral administration is more effective to deliver the BMSCs to the cerebral ischemic lesions than the intravenous administration. SPECT imaging of 111In-oxine labeled BMSCs may be a valuable modality to track the transplanted cells in the host brain non-invasively and serially in clinical situation.

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