Death and Survival in CNS Grafting

Because neurodegenerative diseases have their functional impact as the result of the death of neurons and glia, an obvious strategy is to replace them. This is a particularly attractive proposition in diseases such as Parkinson’s disease (PD) and Huntington’s disease (HD), in which there is loss of a well-defined set of neurons in a small and restricted area of the brain. The prospects are less inviting when there is loss of neurons spread diffusely over the whole central nervous system (CNS) or the whole cortex, because multiple implants of large numbers of cells would probably be required. Glial grafting to defined sites of demyelination is also an attractive prospect for the treatment of multiple sclerosis plaques. There are four potential sources of cells for grafting: cells derived from an adult human donor, cells derived from an embryonic human donor, cells derived from the patient, and embryonic stem cells expanded and differentiated in culture. All these types of cell have been transplanted. For reasons that are not fully under- stood, adult neurons hardly ever survive transplantation, and those that do make no useful connections. Neuronal cells derived from embryos may survive well after transplantation, and may make profuse connections with the host CNS, but only if transplanted at the right stage. The only experience of transplanting autografts into human patients is with grafts of adrenal medulla, intended to treat PD, and there is little evidence of such grafts surviving to provide useful function.