Delayed transplantation of precursor cell‐derived astrocytes provides multiple benefits in a rat model of P arkinsons

In addition to dopaminergic neuron loss, it is clear that Parkinson disease includes other pathological changes, including loss of additional neuronal populations. As a means of addressing multiple pathological changes with a single therapeutically‐relevant approach, we employed delayed transplantation of a unique class of astrocytes, GDA s BMP , that are generated in vitro by directed differentiation of glial precursors. GDA s BMP produce multiple agents of interest as treatments for PD and other neurodegenerative disorders, including BDNF , GDNF , neurturin and IGF 1. GDA s BMP also exhibit increased levels of antioxidant pathway components, including levels of NADPH and glutathione. Delayed GDA BMP transplantation into the 6‐hydroxydopamine lesioned rat striatum restored tyrosine hydroxylase expression and promoted behavioral recovery. GDA BMP transplantation also rescued pathological changes not prevented in other studies, such as the rescue of parvalbumin + GABA ergic interneurons. Consistent with expression of the synaptic modulatory proteins thrombospondin‐1 and 2 by GDA s BMP , increased expression of the synaptic protein synaptophysin was also observed. Thus, GDA s BMP offer a multimodal support cell therapy that provides multiple benefits without requiring prior genetic manipulation. image In vitro ‐generated astrocytes GDA s BMP transplantation is the first example of a multimodal single therapeutic cell therapy approach with the potential to promote recovery of multiple neuron populations of relevance to Parkinson's Disease in a rat model. Transplantation of GDA s BMP provides a successful astrocyte‐based multimodal treatment in a model of Parkinson's Disease without the need for prior genetic modification of cells or the use of neuron transplants to restore function. Recovery of multiple neuronal populations, including tyrosine hydroxylase expressing, dopaminergic neurons and parvalbumin+ GABA ergic interneurons, was caused by post‐symptomatic transplantation of GDA s BMP into a hemiparkinsonian model. Consistent with high levels of expression of the synaptic modulatory proteins thrombospondin 1 and 2 in GDA s BMP , restored expression of the synaptic protein synaptophysin was also seen in the striatum of transplanted animals. Multiple factors of interest for the treatment of neurodegenerative disease, including brain‐ and glia‐derived neurotrophic factor, neurturin and IGF 1 and‐2, are intrinsically produced by GDA s BMP and are produced at l