TY - JOUR
T1 - Cell replacement therapy for central nervous system diseases
AU - Tso, Danju
AU - McKinnon, Randall D.
N1 - Publisher Copyright:
© 2015, Editorial Board of Neural Regeneration Research. All rights reserved.
Copyright:
Copyright 2015 Elsevier B.V., All rights reserved.
PY - 2015
Y1 - 2015
N2 - 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 graft-able 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.
AB - 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 graft-able 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.
KW - Embryonic stem cells
KW - In vivo direct reprogramming
KW - Induced pluripotent stem cell
KW - Personalized medicine
KW - Spinal cord injury
KW - Trauma
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U2 - 10.4103/1673-5374.165209
DO - 10.4103/1673-5374.165209
M3 - Review article
AN - SCOPUS:84942114214
VL - 10
SP - 1356
EP - 1358
JO - Neural Regeneration Research
JF - Neural Regeneration Research
SN - 1673-5374
IS - 9
ER -