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

Hill, Christopher ORCID: 0000-0003-3831-4569 (2020) Assessing Human Embryonic Stem Cell-Derived Dopaminergic Neuron Progenitor Transplants Using Non-invasive Imaging Techniques. Molecular Imaging and Biology, 22 (5). pp. 1244-1254.

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Official URL: http://dx.doi.org/10.1007/s11307-020-01499-4

Abstract

<h4>Purpose</h4>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.<h4>Procedures</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>In summary, our findings support the transplantation of hPSC-derived DAPCs as a safe treatment for PD.

Item Type:	Article
Uncontrolled Keywords:	Dopaminergic neuron progenitor cells, Human pluripotent stem cell, Parkinson's disease, Non-invasive imaging, Bioluminescence, Magnetic resonance imaging
Depositing User:	Symplectic Admin
Date Deposited:	07 May 2020 10:11
Last Modified:	18 Jan 2023 23:52
DOI:	10.1007/s11307-020-01499-4
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3086340