Imaging of human stem cell-derived dopamine grafts correlates with behavioural recovery and reveals microstructural brain changes DOI Creative Commons
Stephen J. Paisey, Lesley Jones, David J. Harrison

и другие.

Neurobiology of Disease, Год журнала: 2025, Номер 209, С. 106910 - 106910

Опубликована: Апрель 14, 2025

Cell therapy is a promising therapeutic intervention for Parkinson's disease (PD) and currently undergoing safety efficacy testing in clinical trials worldwide. The goals of this project were (1) to determine whether [18F]Fluorodopa or [18F]Fallypride imaging correlates robustly with functional recovery; (2) explore diffusion-weighted MR (DWI) could detect graft-induced cytoarchitectural changes the host brain. hfVM hESC-derived dopamine precursor cells transplanted into 6-OHDA lesioned rat striatum. Tests motor function PET conducted up 6 months post-transplantation. Our data demonstrate that identified presynaptic DA synthesis from dopaminergic grafts confirmed occupancy normalisation D2/D3 receptor expression grafted hemisphere. In rats, binding correlated recovery on range drug-induced drug-free behavioural tasks. hESC-DA improvements signals preceded naturalistic behaviours. DWI revealed widespread graft-mediated microstructural rodent brain, which did not identify graft placement, but instead may reflect remodelling neuroglia. These further our understanding impact brain cytoarchitecture potential these radioligands predict aid translation therapeutics preclinical settings.

Язык: Английский

Imaging of human stem cell-derived dopamine grafts correlates with behavioural recovery and reveals microstructural brain changes DOI Creative Commons
Stephen J. Paisey, Lesley Jones, David J. Harrison

и другие.

Neurobiology of Disease, Год журнала: 2025, Номер 209, С. 106910 - 106910

Опубликована: Апрель 14, 2025

Cell therapy is a promising therapeutic intervention for Parkinson's disease (PD) and currently undergoing safety efficacy testing in clinical trials worldwide. The goals of this project were (1) to determine whether [18F]Fluorodopa or [18F]Fallypride imaging correlates robustly with functional recovery; (2) explore diffusion-weighted MR (DWI) could detect graft-induced cytoarchitectural changes the host brain. hfVM hESC-derived dopamine precursor cells transplanted into 6-OHDA lesioned rat striatum. Tests motor function PET conducted up 6 months post-transplantation. Our data demonstrate that identified presynaptic DA synthesis from dopaminergic grafts confirmed occupancy normalisation D2/D3 receptor expression grafted hemisphere. In rats, binding correlated recovery on range drug-induced drug-free behavioural tasks. hESC-DA improvements signals preceded naturalistic behaviours. DWI revealed widespread graft-mediated microstructural rodent brain, which did not identify graft placement, but instead may reflect remodelling neuroglia. These further our understanding impact brain cytoarchitecture potential these radioligands predict aid translation therapeutics preclinical settings.

Язык: Английский

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