[ 18 F]DPA-714 PET imaging shows immunomodulatory effect of intravenous administration of bone marrow stromal cells after transient focal ischemia

Abstract

Background

The potential application of bone marrow stromal cell (BMSC) therapy in stroke has been anticipated due to its immunomodulatory effects. Recently, positron emission tomography (PET) with [¹⁸F]DPA-714, a translocator protein (TSPO) ligand, has become available for use as a neural inflammatory indicator. We aimed to evaluate the effects of BMSC administration after transient middle cerebral artery occlusion (MCAO) using [¹⁸F]DPA-714 PET.

The BMSCs or vehicle were administered intravenously to rat MCAO models at 3 h after the insult. Neurological deficits, body weight, infarct volume, and histology were analyzed. [¹⁸F]DPA-714 PET was performed 3 and 10 days after MCAO.

Results

Rats had severe neurological deficits and body weight loss after MCAO. Cell administration ameliorated these effects as well as the infarct volume. Although weight loss occurred in the spleen and thymus, cell administration suppressed it. In both vehicle and BMSC groups, [¹⁸F]DPA-714 PET showed a high standardized uptake value (SUV) around the ischemic area 3 days after MCAO. Although SUV was increased further 10 days after MCAO in both groups, the increase was inhibited in the BMSC group, significantly. Histological analysis showed that an inflammatory reaction occurred in the lymphoid organs and brain after MCAO, which was suppressed in the BMSC group.

Conclusions

The present results suggest that BMSC therapy could be effective in ischemic stroke due to modulation of systemic inflammatory responses. The [¹⁸F]DPA-714 PET/CT system can accurately demonstrate brain inflammation and evaluate the BMSC therapeutic effect in an imaging context. It has great potential for clinical application.

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