Migration of neurotrophic factors-secreting mesenchymal stem cells towards a quinolinic acid lesion as viewed by MRI

Migration of neurotrophic factors-secreting mesenchymal stem cells towards a quinolinic acid lesion as viewed by MRI.

Laboratory of Neurosciences, FMRC, Department of Neurology, Rabin Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Israel.

Stem cell based treatment is a promising frontier for neurodegenerative diseases. We propose a novel protocol for inducing the differentiation of rat mesenchymal stem cells (MSCs) towards neurotrophic factors (NTFs) secreting cells as a possible neuroprotective agent. One of the major caveats of stem cell transplantation is their fate post transplantation. For that purpose, we tracked the transplanted cells in vivo by MRI scans and validated the results by histology. MSCs went through a two-step medium-based differentiation protocol, followed by in vitro characterization employing immunocytochemistry and immunoblotting analysis of the cells media. We examined the migratory properties of the cells in the quinolinic acid (QA) induced striatal lesion model for Huntington's disease. The induced cells were labeled and transplanted posterior to the lesion. Rats underwent serial MRI scans to detect cell migration in vivo. On the 19th day, animals were sacrificed and their brains were removed for immunostaining. Rat MSCs post induction exhibited both neuronal and astrocyte markers, as well as unregulated production and secretion of NTFs. High resolution 2D and 3D MR images revealed that the cells migrated along a distinct route towards the lesion. The in vivo MRI results were validated by the histological study which demonstrated that phagocytosis had only partially occurred, and that MRI could correctly depict the status of the migrating cells. The results show that these cells migrated towards a QA lesion, and therefore survived for 19 days post transplantation. This gives hope for future research harnessing these cells for treating neurodegenerative diseases.

PMID: 18635865 [PubMed - as supplied by publisher]