Assessing Human Embryonic Stem Cell-Derived Dopaminergic Neuron Progenitor Transplants Using Non-invasive Imaging Techni
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RESEARCH ARTICLE
Assessing Human Embryonic Stem Cell-Derived Dopaminergic Neuron Progenitor Transplants Using Non-invasive Imaging Techniques M. Mousavinejad,1 S. Skidmore,1,2 F. G. Barone,1 P. Tyers,3 V. Pisupati,2 H. Poptani,1 A. Plagge,1 R. A. Barker,2,3 P. Murray,1 A. Taylor,1 C. J. Hill1,4 1
Department of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool, L69 3BX, UK WT-MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK 3 John van Geest Centre for Brain Repair & Department of Neurology, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK 4 Centre for Women’s Health Research, Department of Women’s and Children’s Health, Institute of Translational Medicine, University of Liverpool, Liverpool, L8 7SS, UK 2
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. Key words: Dopaminergic neuron progenitor cells, Human pluripotent stem cell, Parkinson’s disease, Non-invasive imaging, Bioluminescence, Magnetic resonance imaging
Introduction Electronic supplementary material The online version of this article (https:// doi.org/10.1007/s11307-020-01499-4) contains supplementary material, which is available to authorized users. Correspondence to: A. Taylor; e-mail: [email protected], C. Hill; email: [email protected]
Parkinson’s disease (PD) is a neurodegenerative disease that results in part from the progressive loss of dopaminergic (DA) neurons in the substantia nigra. Several groups have shown that human pluripotent stem cell (hPSC)-derived dopaminergic neuron progenitor cells (DAPCs) can generate
Mousavinejad M. et al.: Multimodal imaging of neu
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