Establishing specific cell lineages from human induced pluripotent stem cells (hiPSCs) is vital for cell therapy approaches in regenerative medicine, particularly for neurodegenerative disorders. While neural precursors have been induced from hiPSCs, the establishment of hiPSC-derived human neural stem cells (hiNSCs), with characteristics that match foetal hNSCs and abide by cGMP standards, thus allowing clinical applications, has not been described. We generated hiNSCs by a virus-free technique, whose properties recapitulate those of the clinical-grade hNSCs successfully used in an Amyotrophic Lateral Sclerosis (ALS) phase I clinical trial. Ex vivo, hiNSCs critically depend on exogenous mitogens for stable self-renewal and amplification and spontaneously differentiate into astrocytes, oligodendrocytes and neurons upon their removal. In the brain of immunodeficient mice, hiNSCs engraft and differentiate into neurons and glia, without tumour formation. These findings now warrant the establishment of clinical-grade, autologous and continuous hiNSC lines for clinical trials in neurological diseases such as Huntington’s, Parkinson’s and Alzheimer’s, among others.

Rosati, J., Ferrari, D., Altieri, F., Tardivo, S., Ricciolini, C., Fusilli, C., et al. (2018). Establishment of stable iPS-derived human neural stem cell lines suitable for cell therapies. CELL DEATH & DISEASE, 9(10), 1-16 [10.1038/s41419-018-0990-2].

Establishment of stable iPS-derived human neural stem cell lines suitable for cell therapies

Ferrari, Daniela
Secondo
;
Zalfa, Cristina;Vescovi, Angelo L.
Ultimo
2018

Abstract

Establishing specific cell lineages from human induced pluripotent stem cells (hiPSCs) is vital for cell therapy approaches in regenerative medicine, particularly for neurodegenerative disorders. While neural precursors have been induced from hiPSCs, the establishment of hiPSC-derived human neural stem cells (hiNSCs), with characteristics that match foetal hNSCs and abide by cGMP standards, thus allowing clinical applications, has not been described. We generated hiNSCs by a virus-free technique, whose properties recapitulate those of the clinical-grade hNSCs successfully used in an Amyotrophic Lateral Sclerosis (ALS) phase I clinical trial. Ex vivo, hiNSCs critically depend on exogenous mitogens for stable self-renewal and amplification and spontaneously differentiate into astrocytes, oligodendrocytes and neurons upon their removal. In the brain of immunodeficient mice, hiNSCs engraft and differentiate into neurons and glia, without tumour formation. These findings now warrant the establishment of clinical-grade, autologous and continuous hiNSC lines for clinical trials in neurological diseases such as Huntington’s, Parkinson’s and Alzheimer’s, among others.
Articolo in rivista - Articolo scientifico
Immunology; Cellular and Molecular Neuroscience; Cell Biology; Cancer Research
English
2018
9
10
1
16
937
open
Rosati, J., Ferrari, D., Altieri, F., Tardivo, S., Ricciolini, C., Fusilli, C., et al. (2018). Establishment of stable iPS-derived human neural stem cell lines suitable for cell therapies. CELL DEATH & DISEASE, 9(10), 1-16 [10.1038/s41419-018-0990-2].
File in questo prodotto:
File Dimensione Formato  
10281-219101.pdf

accesso aperto

Tipologia di allegato: Publisher’s Version (Version of Record, VoR)
Dimensione 3.93 MB
Formato Adobe PDF
3.93 MB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/219101
Citazioni
  • Scopus 32
  • ???jsp.display-item.citation.isi??? 31
Social impact