Neural stem cells as therapeutics and cellular models of disease
Neural stem cells have considerable potential as therapeutic agents in their own right, but also as models of the pathophysiology of brain disease. We have used two approaches to generate human neural stem cells: conditional immortalisation, and somatic cell reprogramming (iPS cells). We have demonstrated that the conditionally-immortalised cells have efficacy in animal models of stroke and spinal cord injury. In this presentation, I outline those data, and describe the pathway that has led to the investigation of the efficacy of these cells in clinical trials in stroke. The challenge currently is to understand the mode of action of these cells, and I describe experiments that indicate an effect of engraftment on endogenous repair mechanisms. In further studies, we have attempted to enhance the tissue reconstruction capacity of these cells by combining them with matrices. I also describe the challenge to the use of these cells posed by the intrinsic diversity of neural stem cell populations, and the potential of the cells to model disease in culture.
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