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

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Mousavinejad, M. 
Skidmore, S. 
Barone, F. G. 
Tyers, P. 
Pisupati, V. 


Abstract: 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.



Research Article, Dopaminergic neuron progenitor cells, Human pluripotent stem cell, Parkinson’s disease, Non-invasive imaging, Bioluminescence, Magnetic resonance imaging

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Molecular Imaging and Biology

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Springer International Publishing
UK Regenerative Medicine Platform (MR/K026739/1)