Assessing Human Embryonic Stem Cell-Derived Dopaminergic Neuron Progenitor Transplants Using Non-invasive Imaging Techniques.

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Mousavinejad, M 
Skidmore, S 
Barone, FG 
Tyers, P 
Pisupati, V 

PURPOSE: Human pluripotent stem cell (hPSC)-derived dopaminergic neuron progenitor cells (DAPCs) are a potential therapy for Parkinson's disease (PD). However, their intracranial administration raises safety concerns including uncontrolled proliferation, migration and inflammation. Here, we apply a bimodal imaging approach to investigate the fate of DAPC transplants in the rat striatum. PROCEDURES: DAPCs co-expressing luciferase and ZsGreen or labelled with micron-sized particles of iron oxide (MPIOs) were transplanted in the striatum of RNU rats (n = 6 per group). DAPCs were tracked in vivo using bioluminescence and magnetic resonance (MR) imaging modalities. RESULTS: Transgene silencing in differentiating DAPCs accompanied with signal attenuation due to animal growth rendered the bioluminescence undetectable by week 2 post intrastriatal transplantation. However, MR imaging of MPIO-labelled DAPCs showed that transplanted cells remained at the site of injection for over 120 days. Post-mortem histological analysis of DAPC transplants demonstrated that labelling with either luciferase/ZsGreen or MPIOs did not affect the ability of cells to differentiate into mature dopaminergic neurons. Importantly, labelled cells did not elicit increased glial reactivity compared to non-labelled cells. CONCLUSIONS: In summary, our findings support the transplantation of hPSC-derived DAPCs as a safe treatment for PD.

Bioluminescence, Dopaminergic neuron progenitor cells, Human pluripotent stem cell, Magnetic resonance imaging, Non-invasive imaging, Parkinson’s disease, Animals, Brain, Carcinogenesis, Cell Differentiation, Cell Line, Dopaminergic Neurons, Ferric Compounds, Genes, Reporter, Glial Fibrillary Acidic Protein, Human Embryonic Stem Cells, Humans, Luminescent Measurements, Magnetic Resonance Imaging, Male, Neural Stem Cells, Neuroglia, Particle Size, Rats, Stem Cell Transplantation
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Mol Imaging Biol
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Springer Science and Business Media LLC
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Medical Research Council (MC_PC_12009)
Medical Research Council (MC_PC_17230)
UK Regenerative Medicine Platform (MR/K026739/1)