The brain and spinal cord can not replace neurons or supporting glia that are lost through traumatic injury or disease. In pre-clinical studies, however, neural stem and progenitor cell transplants can promote functional recovery. Thus the central nervous system is repair competent but lacks endogenous stem cell resources. To make transplants clinically feasible, this field needs a source of histocompatible, ethically acceptable and non-tumorgenic cells. One strategy to generate patient-specific replacement cells is to reprogram autologous cells such as fibroblasts into pluripotent stem cells which can then be differentiated into the required cell grafts. However, the utility of pluripotent cell derived grafts is limited since they can retain founder cells with intrinsic neoplastic potential. A recent extension of this technology directly reprograms fibroblasts into the final graftable cells without an induced pluripotent stem cell intermediate, avoiding the pluripotent caveat. For both types of reprogramming the conversion efficiency is very low resulting in the need to amplify the cells in culture which can lead to chromosomal instability and neoplasia. Thus to make reprogramming biology clinically feasible, we must improve the efficiency. The ultimate source of replacement cells may reside in directly reprogramming accessible cells within the brain.
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