Millipore tech unravels neural degeneration
The study, published in the open access journal PLoS ONE, established the first functional link between the PINK1 gene and the neural degeneration observed in Parkinson's disease (PD).
The research, conducted by Dr Alison Wood-Kaczmar, Dr Sarah Tabrizi, Professor Nick Wood and colleagues at the Institute of Neurology in London, UK, showed that the ReNcell VM stem cell line can be used to model the pathogenesis of certain inherited forms of PD.
PD is the most common neurodegenerative motor disorder in the Western world and is clinically characterized by resting tremors, rigidity and slowness of movement. Symptoms have been found to be partially alleviated by the administration of exogenous dopamine (L-dopa).
The researchers showed that suppressing the PINK1 gene in neurons derived from the ReNcell VM stem cell line using RNAi techniques resulted in reduced long term viability of the neurons, which die via the mitochondrial apoptosis pathway.
The PINK1 deficient neurons demonstrated features of marked oxidative stress with widespread mitochondrial dysfunction and abnormal mitochondrial morphology.
The phenotypic results obtained by the researchers with the human neurons were mirrored in control studies on primary neurons derived from transgenic PINK1 knockout mice.
The results of the suppression studies indicate that PINK1 plays a neuroprotective role in the mitochondria of mammalian neurons, especially against stress causing agents such as staurosporine.
Additionally, the researchers found that cellular compensatory mechanisms such as mitochondrial biogenesis and upregulation of lysosomal degradation pathways occur in the absence of the PINK1 gene.
"This latest publication is an elegant example of how ReNeuron's ReNcell lines can be readily modified and used to model human neurodegenerative disease in a dish," said ReNeuron's chief scientific officer, Dr John Sinden.
"The model described in this paper represents an in vitro system highly relevant to human Parkinson's disease, which can be generated at lower cost and with greater species relevance than could be achieved using a transgenic animal model."
The ReNcell VM neural stem cell line was developed by ReNeuron, and can be readily differentiated into all three neural lineages (neurons, astrocytes, and oligodendrocytes).
According to the firm it was the first marketed human neural progenitor line, under license to Millipore, and is the first tissue-specific cell line that can grow stably in the laboratory as a pure population of stem cells without ongoing differentiation that can be grown as a monolayer in serum-free culture media.
