Clinical Research; Research Networks; Laboratory Based Research


Click on each link below to find out more:

Behavioural research (led by Prof Steve Dunnett)
Clinical neuroscience (led by Prof Anne Rosser)
Genetics research group/stemcell theraphy (led by Dr Nick Allen)
Molecular research (led by Dr Lesley Jones)

Genetics research group/stemcell theraphy (led by Dr Nick Allen)

Embryonic Stem Cell Derived Neurons for Striatal Repair

Embryonic stem (ES) cells are quite remarkable. They are true stem cells that can be expanded indefinitely in culture to generate vast numbers of cells, and yet they have the capacity to respond to different developmental cues and differentiate to become any one of the diverse cell types that make up the human body. For this reason ES cells are rightly receiving enormous research interest in the field of regenerative medicine.
ES cells are of particular interest to Huntington’s disease in two vital areas. First, by applying neural differentiation protocols, ES cells have the potential of providing suitable neural tissue for brain repair by cell transplantation, and second, the availability of human neurons, derived from ES cells, will become vital tools for high throughput screens in future drug discovery programmes.
For both applications, underpinning technology needs to be developed that works to control and direct the differentiation of ES cells first to neural precursors and then specifically to derive neurons with the functional properties of striatal medium spiny neurons, those neurons that are most severely affected in Huntington’s disease. In our lab we are working with both human and mouse ES cells. A significant achievement has been to establish protocols that generate functional neurons with very high efficiency in completely defined cell culture medium. Our emphasis on defining all components of the culture system will be particularly important in future work that will hopefully bring ES cell differentiation towards clinical application.
Despite the success in generating significant neural populations from ES cells further work is still required to manipulate the cells neural differentiation programme. Transplant studies (web link to Steve!) have determined that successful transplantation requires donor cells to be developmentally programmed to express ventral forebrain characteristics, and that neural tissue derived from other developing brain regions is not sufficiently adaptable to generate functional grafts. The progenitor cells to striatal neurons can be identified by their expression of specific ventral forebrain-restricted genes, and we are using these genes as markers to identify and enrich for striatal progenitor cells in differentiated ES cell cultures.

1. Human ES cell derived neural progenitors propagated as neurospheres in bulk culture	2. Linear expansion leads to  large scale production of neural progenitor cells
3. In vitro differentiation of hECSs expressing the mutant gene for Huntington’s disease could be used to generate large numbers of human neurons for biochemical studies of the disease process and for drug screening	4. Human ES cell derived neurons are electrically active
5. Human ES cell derived neurons undergo neural differentiation in striatal grafts

Group members:
Nick Allen
Alysia Battersby
Sophie Precious

Collaborators:
Cambridge University Centre for Brain Repair
Siddharthan Chandran
Alexis Joannides

INSERM
Marc Peschanski

Bristol University
James Uney