Imaging of human stem cell-derived dopamine grafts correlates with behavioural recovery and reveals microstructural brain changes.

Cell therapy is a promising therapeutic intervention for Parkinson's disease (PD) and is currently undergoing safety and efficacy testing in clinical trials worldwide. The goals of this project were (1) to determine whether [F]Fluorodopa or [F]Fallypride imaging correlates robustly with functional recovery; and (2) to explore whether diffusion-weighted MR imaging (DWI) could detect graft-induced cytoarchitectural changes in the host brain. hfVM and hESC-derived dopamine precursor cells were transplanted into the 6-OHDA lesioned rat striatum.

Cryopreservation of Human Midbrain Dopaminergic Neural Progenitor Cells Poised for Neuronal Differentiation.

Human pluripotent stem cells can be differentiated into midbrain dopaminergic (mDA) neurons by directing cells through a floor plate progenitor stage. The developmental identity of mDA neurons produced using floor plate protocols is similar to neurons, and this has improved the ability to model Parkinson's disease (PD) in a dish. Combined with the unlimited growth potential of pluripotent stem cells, mDA neural progenitor cell production can provide a scalable source of human dopaminergic (DA) neurons for diverse applications.

Engineering synucleinopathy-resistant human dopaminergic neurons by CRISPR-mediated deletion of the SNCA gene.

An emerging treatment for Parkinson's disease (PD) is cell replacement therapy. Authentic midbrain dopaminergic (mDA) neuronal precursors can be differentiated from human embryonic stem cells (hESCs) and human induced pluripotent stem cells (iPSCs). These laboratory-generated mDA cells have been demonstrated to mature into functional dopaminergic neurons upon transplantation into preclinical models of PD.

A synthetic cell permeable antioxidant protects neurons against acute oxidative stress.

Excessive reactive oxygen species (ROS) can damage proteins, lipids, and DNA, which result in cell damage and death. The outcomes can be acute, as seen in stroke, or more chronic as observed in age-related diseases such as Parkinson's disease. Here we investigate the antioxidant ability of a novel synthetic flavonoid, Proxison (7-decyl-3-hydroxy-2-(3,4,5-trihydroxyphenyl)-4-chromenone), using a range of in vitro and in vivo approaches.