Bone-marrow mononuclear cells reduce neurodegeneration in hippocampal CA1 layer after transient global ischemia in rats.

Global cerebral ischemia (GCI) results in death of the pyramidal neurons in the CA1 layer of the hippocampus. In this study we used the four-vessel occlusion (4VO) model of GCI to investigate a potential neuroprotective role of bone-marrow mononuclear cells (BMMCs) transplantation. BMMCs (3×10(7)) were injected through the carotid artery, 1 or 3 days after ischemia (DAI), and the number of cells undergoing degeneration was investigated in brains at 7 DAI. A significant decrease in the number of dying cells was observed in the treated group, compared to animals treated with saline. Biodistribution of the injected cells (1 or 3 DAI) was investigated by (99m)Technetium labeling of the BMMCs and subsequent image analysis 2h after transplantation. In addition, the presence of CellTrace(™)-labeled BMMCs was investigated in tissue sections of the hippocampal area of these transplanted animals. BMMCs treatment significantly reduced the number of FJ-C positive cells in the hippocampal CA1 layer at 7 DAI. We also observed a decrease in the number of activated microglia/macrophage (ED1-positive cells) in the BMMCs-treated group compared with the untreated group. Our data show that BMMCs are able to modulate the microglial response and reduce neurodegeneration in the CA1 layer.

Neuroprotective effects and magnetic resonance imaging of mesenchymal stem cells labeled with SPION in a rat model of Huntington's disease.

Bone marrow mesenchymal stem cells (MSC) have been tested and proven effective in some neurodegenerative diseases, but their tracking after transplantation may be challenging. Our group has previously demonstrated the feasibility and biosafety of rat MSC labeling with iron oxide superparamagnetic nanoparticles (SPION). In this study, we investigated the therapeutic potential of SPION-labeled MSC in a rat model of Huntington's disease, a genetic degenerative disease with characteristic deletion of striatal GABAergic neurons. MSC labeled with SPION were injected into the striatum 1h after quinolinic acid injection. FJ-C analysis demonstrated that MSC transplantation significantly decreased the number of degenerating neurons in the damaged striatum 7 days after lesion. In this period, MSC transplantation enhanced the striatal expression of FGF-2 but did not affect subventricular zone proliferation, as demonstrated by Ki67 proliferation assay. In addition, MSC transplantation significantly reduced the ventriculomegaly in the lesioned brain. MRI and histological techniques detected the presence of the SPION-labeled cells at the lesion site. SPION-labeled MSC produced magnetic resonance imaging (MRI) signals that were visible for at least 60 days after transplantation. Our data highlight the potential of adult MSC to reduce brain damage under neurodegenerative diseases and indicate the use of nanoparticles in cell tracking, supporting their potential as valuable tools for cell therapy.