Induced neural stem cells: methods of reprogramming and potential therapeutic applications.
Developmental studies and experimental data have enabled us to assert that the terminal cell differentiation state is reversible, and that altering the balance of specific transcription factors could be a powerful strategy for inducing pluripotency. Due to the risks related to using induced pluripotent cells in clinical applications, biologists are now striving to develop methods to induce a committed differentiated cell type by direct conversion of another cell line. Several reprogramming factors have been discovered, and some cellular phenotypes have been obtained by novel transdifferentiation processes. It has been recently demonstrated that induced neural stem cells (iNSCs) can be obtained from rodent and human somatic cells, like fibroblasts, through the forced expression of defined transcription factors. To date, two different approaches have been successfully used to obtain iNSCs: a direct method and an indirect method that involves an intermediate destabilized state. The possibility to induce characterized iNSCs from human cells, e.g. fibroblasts, has opened new horizons for research in human disease modelling and cellular therapeutic applications in the neurological field. This review focuses on reported reprogramming techniques and innovative techniques that can be further explored in this area, as well as on the criteria for the phenotypic characterization of iNSCs and their use in developing novel therapeutic strategies for neurological diseases.
Dino Ferrari Centre, Department of Neurological Sciences, University of Milan, IRCCS Foundation Ca'Granda Maggiore Hospital Policlinico, Milan, Italy.
Margherita
M
Ruggieri
Dino Ferrari Centre, Department of Neurological Sciences, University of Milan, IRCCS Foundation Ca'Granda Maggiore Hospital Policlinico, Milan, Italy.
Giulietta
G
Riboldi
Dino Ferrari Centre, Department of Neurological Sciences, University of Milan, IRCCS Foundation Ca'Granda Maggiore Hospital Policlinico, Milan, Italy.
Simona
S
Brajkovic
Dino Ferrari Centre, Department of Neurological Sciences, University of Milan, IRCCS Foundation Ca'Granda Maggiore Hospital Policlinico, Milan, Italy.
Monica
M
Bucchia
Dino Ferrari Centre, Department of Neurological Sciences, University of Milan, IRCCS Foundation Ca'Granda Maggiore Hospital Policlinico, Milan, Italy; IRCCS Eugenio Medea, Bosisio Parini, Lecco, Italy.
Nereo
N
Bresolin
Dino Ferrari Centre, Department of Neurological Sciences, University of Milan, IRCCS Foundation Ca'Granda Maggiore Hospital Policlinico, Milan, Italy.
Giacomo P
GP
Comi
Dino Ferrari Centre, Department of Neurological Sciences, University of Milan, IRCCS Foundation Ca'Granda Maggiore Hospital Policlinico, Milan, Italy. Electronic address: stefania.corti@unimi.it.
Stefania
S
Corti
D000818:Animals; D001927:Brain Diseases / Q000628:therapy*; D002454:Cell Differentiation; D006801:Humans; D058953:Neural Stem Cells / Q000502:physiology* / Q000637:transplantation*
Clinical application; Induced neural stem cells; Multipotency; Reprogramming; Self-renewal