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

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.

journal_name

Mol Imaging Biol

journal_title

Molecular imaging and biology

authors

Mousavinejad M,Skidmore S,Barone FG,Tyers P,Pisupati V,Poptani H,Plagge A,Barker RA,Murray P,Taylor A,Hill CJ

doi

10.1007/s11307-020-01499-4

subject

Has Abstract

pub_date

2020-10-01 00:00:00

pages

1244-1254

issue

5

eissn

1536-1632

issn

1860-2002

pii

10.1007/s11307-020-01499-4

journal_volume

22

pub_type

杂志文章

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