Abstract
Dedifferentiation, as one of the mechanisms rerouting cell fate, regresses cells from a differentiated status to a more primitive one. Due to its potential of amplifying the stem/progenitor cell pool and reproducing sizable and desirable cellular elements, it has been attended in the field of regenerative medicine, which will hopefully provide novel therapeutic strategies for currently incurable diseases, such as varieties of central nervous system (CNS) diseases and injuries. In this article, we will first discuss naturally occurring and experimentally induced dedifferentiation, and then set forth principles in stem-cell based therapy in the neural field; beyond that, we will introduce two recent studies that show dedifferentiated stem cells contribute to neural regeneration. Moreover, we also present our recent research results of dedifferentiated muscle stem cells for neurogenic differentiation study in vitro. Further work will be conducted to elucidate the mechanism underlying the dedifferentiation process to facilitate the development of new strategies in regenerative medicine.
Highlights
Dedifferentiation, as one of the mechanisms rerouting cell fate, regresses cells from a differentiated status to a more primitive one
Most recently, using an ingenious cre/lox system, our research demonstrated for the first time that dedifferentiation of skeletal muscle cells to early progenitor cells, including myoblasts and muscle-derived stem cells (MDSCs), occurs in an injured mouse model in vivo and can enhance cell proliferation and myogenesis [34]
The meaning of the word “regeneration” in central nervous system (CNS) could be extended from axonogenesis and synaptogenesis to the replacement of lost cells with newly generated elements coming from stem/progenitor cells, i.e., adult neurogenesis
Summary
With respect to other organs, the CNS shows structural peculiarities, and owing to the relative lack of recovery from CNS injury, the dogmatic view of a “fixed, ended and immutable” neural tissue in mammals has been prevalent since the early 1900s [43,44,45]. The meaning of the word “regeneration” in CNS could be extended from axonogenesis and synaptogenesis to the replacement of lost cells with newly generated elements coming from stem/progenitor cells, i.e., adult neurogenesis Such a possibility for cell renewal theoretically brings our nervous system into the context of regenerative medicine. Local progenitors that are in a relatively quiescent state in layer I of the rat cerebral cortex were activated after ischemia, giving rise to new cortical interneurons [86] These examples support the hypothesis that the mature CNS parenchyma may retain a latent stem/progenitor cell potential that is normally inhibited in vivo, but that, if properly evoked, might be exploited in situ for cell replacement
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