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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2018-09-17

AUTHORS

Jessica Rosati, Daniela Ferrari, Filomena Altieri, Silvia Tardivo, Claudia Ricciolini, Caterina Fusilli, Cristina Zalfa, Daniela C. Profico, Francesca Pinos, Laura Bernardini, Barbara Torres, Isabella Manni, Giulia Piaggio, Elena Binda, Massimiliano Copetti, Giuseppe Lamorte, Tommaso Mazza, Massimo Carella, Maurizio Gelati, Enza Maria Valente, Antonio Simeone, Angelo L. Vescovi

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. More... »

PAGES

937

Journal

TITLE

Cell Death & Disease

ISSUE

10

VOLUME

9

Author Affiliations

  • Cellular Reprogramming Unit, IRCCS Casa Sollievo della Sofferenza, Viale dei Cappuccini, 71013 San Giovanni Rotondo, Foggia Italy
  • Department of Biotechnology and Biosciences, University of Milan Bicocca, Piazza della Scienza, 220126 Milan, Italy
  • Neurogenetics Unit, IRCCS Santa Lucia Foundation, Rome, Italy
  • Stem Cell Laboratory, Cell Factory e Biobank, Terni Hospital, Via Tristano di Joannuccio 1, 05100 Terni, Italy
  • Bioinformatics Unit, IRCCS Casa Sollievo della Sofferenza, Viale dei Cappuccini, 71013 San Giovanni Rotondo, Foggia Italy
  • Production Unit of Advanced Therapies (UPTA), Institute for Stem-Cell Biology, Regenerative Medicine and Innovative Therapies (ISBReMIT), IRCCS Casa Sollievo della Sofferenza, Viale dei Cappuccini, 71013 San Giovanni Rotondo, Foggia Italy
  • Medical Genetics Unit, IRCCS Casa Sollievo della Sofferenza, Viale dei Cappuccini, 71013 San Giovanni Rotondo, Foggia Italy
  • Department of Research, Diagnosis and Innovative Technologies, Regina Elena National Cancer Institute, Rome, Italy
  • Cancer Stem Cells Unit (ICS), Institute for Stem-Cell Biology, Regenerative Medicine and Innovative Therapies (ISBReMIT), IRCCS Casa Sollievo della Sofferenza, Viale dei Cappuccini, 71013 San Giovanni Rotondo, Foggia Italy
  • Biostatistic Unit, IRCCS Casa Sollievo della Sofferenza, Viale dei Cappuccini, 71013 San Giovanni Rotondo, Foggia Italy
  • Department of Molecular Medicine, University of Pavia, Via Forlanini 14, 27100 Pavia, Italy
  • IRCSS Neuromed, 86077 Pozzilli, Isernia Italy
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41419-018-0990-2

    DOI

    http://dx.doi.org/10.1038/s41419-018-0990-2

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1107044739

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/30224709


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