Stem cell transplantation in treating cerebellar cell loss in Hirschsprung’s disease

Although surgery is a life saving procedure for patients with Hirschsprung’s disease, many also exhibit profound neurological disorders, including Downs syndrome, congenital central hypoventilation, nerve related deafness, seizures and mental retardation. Our previous study in a rat model of Hirschsprung’s disease also showed a marked deficit in nerve cell numbers in part of the brain called the cerebellum. We aim to correct this nerve deficit by transplanting healthy stem cells that can develop into nerve cells and glial cells in the diseased cerebellum. We will isolate stem cells from the cerebellum of normal neonatal rats and genetically label the cells with a green protein. These labelled cells will grow into a ball of cells called neurosphere, which will be transplanted into the diseased cerebellum of rats with Hirschsprung’s disease. To allow for the development of neurospheres into functional nerve cells and glial cells, an artificial opening of the gut (stoma) will be created to allow the recipient rats to survive into adulthood. We will analyse the growth and connections made by transplanted cells in the recipient cerebellum using specific labelling techniques, and analyse the restoration of cerebellar functional deficits after stem cell transplantation. The results will provide important information on how the stem cell technique be used for the treatment of brain anomalies in human Hirschsprung’s disease.