Abstract
BackgroundThe 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.ResultsRats 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.ConclusionsThe 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.
Highlights
The potential application of bone marrow stromal cell (BMSC) therapy in stroke has been anticipated due to its immunomodulatory effects
Using a translocator protein (TSPO) ligand [18F]DPA-714 positron emission tomography (PET)/CT system in the present study, we aim to investigate the relationship between stroke and inflammation, and to clarify the immunomodulation ability of BMSCs in post-ischemic inflammation
Distribution of BMSCs in organs Following EdU staining, fluorescence micrographs demonstrated that approximately 60% of BMSCs were labeled
Summary
The potential application of bone marrow stromal cell (BMSC) therapy in stroke has been anticipated due to its immunomodulatory effects. Tan et al EJNMMI Research (2018) 8:35 reducing stroke-associated injury and restoring neural function has become a burning problem that needs to be solved urgently With this intention, the potential of cell-based therapy is being explored. Bone marrow stromal cells (BMSCs), multipotent progenitors with the ability to differentiate into various types of cell lineages, have been considered to have potential application in ischemic stroke therapy These cells can be harvested from the patient, cause no immunological reactions, and have a remarkable capacity for extensive expansion in vitro [6,7,8,9]. We propose the following hypothesis: if ischemic injury occurs, especially following ischemia–reperfusion, proinflammatory cytokines produced by the activated microglia are released into the systemic circulation where they stimulate immune organs These immune organs drive inflammation-mediated damage, thereby inducing more severe brain damage. The rapid use of BMSCs, with the stem cells distributing to lymphoid organs and the brain, could act to downregulate the hyperinflammatory response and upregulate repair processes
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