Stem Cell Neurogenesis

Lead Research Organisation: MRC London Institute of Medical Sciences

Abstract

Parkinsons disease is a progressive and currently incurable neurological disorder that results from the degeneration of a specific type of brain cells called dopaminergic neurons from the midbrain. Transplantation of foetal midbrain tissues in Parkinsons disease patients has shown promising clinical benefit in some patients. However, several difficulties persist which prevent this procedure from being provided routinely and on a mass scale. Some of these difficulties are associated with the fact that we do not have the knowledge required to make the transplanted cells survive well and connect within the brain.||Dopaminergic cells are born during foetal development and the set of gene products they possess determines what type of cells they are. It may be very important that the grafted cells have to have the same set of gene products as the native dopaminergic cells. In this research programme, we plan to perform a series of experiments to determine a list of genes that dopaminergic neurons normally have and to work out how these molecules help with the normal life of a dopaminergic nerve cell. Importantly, we will apply these molecules to direct stem cell differentiation to a dopaminergic pathway. This will have implications for the potential application of stem cells in pharmaceutical and cell based therapies for Parkinsons disease.|

Technical Summary

Parkinsons disease (PD) is a terminal progressive neurodegenerative disorder that affects 120,000 individuals in the UK alone. Most therapeutic strategies attempt to augment declining nigrostriatal dopamine function with drug or cell-based dopamine replacement strategies. However, the development of therapeutic paradigms via either approach is limited by a lack of sufficient understanding of the cellular and molecular mechanisms underlying differential vulnerability of substantia nigra dopaminergic (DA) neurons.||Our objectives therefore are to understand the molecular make up of the midbrain DA lineage, to investigate the roles played by these molecules in midbrain development, and to apply these molecules in promoting DA fate determination and axon growth in stem cells.||We have in the past generated a number of embryonic stem cell lines and animal models that allow specific labelling of DA neuronal progenitors and mature DA neurons in vitro and in vivo. Exploiting these tools has lead to the identification of novel gene markers for midbrain DA neuronal stem cells and mature DA neurons, as well as new factors regulating the specification of DA neuronal lineage. Our current study aims to elucidate the molecular mechanisms by which these factors work. This will have important implications in developing novel target to push stem cells towards a dopaminergic fate in the laboratory which provides as the foundation for realising their potential in modelling disease, pharmaceutical drug screen and cell based therapies. |

Publications

10 25 50
 
Description EC FP7 funding
Amount £500,000 (GBP)
Organisation European Commission 
Department Seventh Framework Programme (FP7)
Sector Public
Country European Union (EU)
Start 12/2008 
End 11/2012
 
Title Cell lines 
Description Dopamine neuron reporter cell lines 
Type Of Material Cell line 
Year Produced 2006 
Provided To Others? Yes  
Impact Provided as powerful tool for transplantation and physiological recording of midbrain dopamine neurons 
 
Description Visit to Univerty of the 3rd age, schools etc 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Primary Audience Schools
Results and Impact talks to school children on stem cells

don't know
Year(s) Of Engagement Activity 2009