Assessing Human Embryonic Stem Cell-Derived Dopaminergic Neuron Progenitor Transplants Using Non-invasive Imaging Techniques.
Mol Imaging Biol
; 22(5): 1244-1254, 2020 10.
Article
em En
| MEDLINE
| ID: mdl-32378000
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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Imageamento por Ressonância Magnética
/
Transplante de Células-Tronco
/
Células-Tronco Neurais
/
Neurônios Dopaminérgicos
/
Células-Tronco Embrionárias Humanas
/
Medições Luminescentes
Limite:
Animals
/
Humans
/
Male
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article