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


Type
Article
Change log
Authors
Mousavinejad, M 
Skidmore, S 
Barone, FG 
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.

Description
Keywords
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
Journal Title
Mol Imaging Biol
Conference Name
Journal ISSN
1536-1632
1860-2002
Volume Title
22
Publisher
Springer Science and Business Media LLC
Rights
All rights reserved
Sponsorship
Medical Research Council (MC_PC_12009)
Medical Research Council (MC_PC_17230)
UK Regenerative Medicine Platform (MR/K026739/1)