Endocrine Abstracts

Neurodegenerative diseases are characterised by the loss of specific subsets of neurons, and whilst drug therapies exist for some of these disorders (eg Parkinson's disease) none of them are curative. This has led to the search for a cell-based therapy, the most successful being the transplantation of human fetal tissue into Parkinson's patients. However, there are ethical and logistical problems associated with this tissue collection, hence an alternative source has been sought. Human neural stem cells (HNSC's) are one such alternative. These cells can be passaged as neurospheres long term in culture and are capable of giving rise to large numbers of neurons in vitro^1,2. In some neurodegenerative disorders, such as Alzheimer's Disease, there is a global neuronal loss, therefore the reported migratory capacity of transplanted neural stem cells and stem cell lines may be beneficial3. In other neurodegenerative disorders the primary pathology is more localized, e.g. Parkinson's Disease and manipulation of stem cells to decrease their migratory capacity prior to transplantation results in more localised tissue replacement. It is possible to increase neuronal differentiation from neurospheres using neurotrophic factors. For transplantation studies, a lesion was created by injecting 6OHDA into the striatum of adult rats. 7 days later human neurospheres which had been maintained in culture for 10 months were trypsinized and injected as a cell suspension into the substantia nigra. One group of animals received cells that had been predifferentiated for 7 days. This involves plating intact neurospheres for 7 days on a laminin substrate in the presence of NT4. This procedure greatly increases the numbers of neurons in these cultures². Another group received undifferentiated cells. Animals were sacrificed 12 weeks following transplantation. Predifferentiation resulted in significantly less migration than that observed with undifferentiated cells and also greatly increased the number of neurons in the transplants.

1. Svendsen et al., J. Neurosci. Meth 1998; 85: 141-152

2. Caldwell MA et al., Nat Biotech 2001; 19: 475-9.

3. Fricker et al. J. Neurosci 1999; 19: 5990-6005.