Migration of neurotrophic factors-secreting mesenchymal stem cells toward a quinolinic acid lesion as viewed by magnetic resonance imaging.
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) toward neurotrophic factor (NTF)-secreting cells as a possible neuroprotective agent. One of the major caveats of stem cell transplantation is their fate post-transplantation. To test the viability of the cells, we tracked the transplanted cells in vivo by magnetic resonance imaging (MRI) scans and validated the results by histology. MSCs went through a two-step medium-based differentiation protocol, followed by in vitro characterization using immunocytochemistry and immunoblotting analysis of the cell 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 postinduction exhibited both neuronal and astrocyte markers, as well as production and secretion of NTFs. High-resolution two-dimensional and three-dimensional magnetic resonance images revealed that the cells migrated along a distinct route toward 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 toward a QA lesion and therefore survived for 19 days post-transplantation. This gives hope for future research harnessing these cells for treating neurodegenerative diseases. Disclosure of potential conflicts of interest is found at the end of this article.
Sadan
Ofer
O
Department of Neurology, Sackler Faculty of Medicine, Laboratory of Neurosciences, Felsenstein Medical Research Center, Petah Tikva, Israel.
Shemesh
Noam
N
Barzilay
Ran
R
Bahat-Stromza
Merav
M
Melamed
Eldad
E
Cohen
Yoram
Y
Offen
Daniel
D
D000818:Animals; D002454:Cell Differentiation; D002465:Cell Movement; D002540:Cerebral Cortex / Q000473:pathology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism*; D017072:Neostriatum / Q000473:pathology*; D009414:Nerve Growth Factors / Q000378:metabolism*; D017378:Quinolinic Acid; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D009414:Nerve Growth Factors; D017378:Quinolinic Acid