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Review ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Neurosci. | doi: 10.3389/fnins.2019.00684

Pluripotent stem cells for brain repair: protocols and preclinical applications in cortical and hippocampal pathologies

 Claudia Alia1*, Marco Terrigno2, Irene Busti1, 3, Federico Cremisi2, 4 and Matteo Caleo1, 5, 6
  • 1Institute of Neuroscience (CNR), Italy
  • 2Scuola Normale Superiore di Pisa, Italy
  • 3Department of Neurosciences, Psychology, Drugs and Child Health Area, School of Psychology, University of Florence, Italy
  • 4Biophysics Institute (IBF) CNR, Italy
  • 5Department of Biomedical Sciences, School of Medicine and Surgery, University of Padova, Italy
  • 6Padova Neuroscience Center, University of Padua, Italy

Brain injuries causing chronic sensory or motor deficit, such as stroke, are among the leading causes of disability worldwide, according to the World Health Organization; furthermore, they carry heavy social and economic burdens due to decreased quality of life and need of assistance. Given the limited effectiveness of rehabilitation, novel therapeutic strategies are required to enhance functional recovery. Since cell-based approaches have emerged as an intriguing and promising strategy to promote brain repair, many efforts have been made to study the functional integration of neurons derived from pluripotent stem cells (PSCs), or fetal neurons, after grafting into the damaged host tissue.
PSCs hold great promises for their clinical applications, such as cellular replacement of damaged neural tissues with autologous neurons. They also offer the possibility to create in vitro models to assess the efficacy of drugs and therapies. Notwithstanding these potential applications, PSC-derived transplanted neurons have to match the precise sub-type, positional and functional identity of the lesioned neural tissue. Thus, the requirement of highly specific and efficient differentiation protocols of PSCs in neurons with appropriate neural identity constitutes the main challenge limiting the clinical use of stem cells in the near future.
In this Review, we discuss the recent advances in the derivation of telencephalic (cortical and hippocampal) neurons from PSCs, assessing specificity and efficiency of the differentiation protocols, with particular emphasis on the genetic and molecular characterization of PSC-derived neurons. Second, we address the remaining challenges for cellular replacement therapies in cortical brain injuries, focusing on electrophysiological properties, functional integration and therapeutic effects of the transplanted neurons.

Keywords: Pluripotent stem cells (PSC), Stroke, Cortex, Hippocampus, Cell-based therapy (CBT), Brain Injuries, brain repair, Differentiation protocol

Received: 15 May 2019; Accepted: 14 Jun 2019.

Edited by:

Johannes Boltze, University of Warwick, United Kingdom

Reviewed by:

Zaal Kokaia, Lund Stem Cell Center, Sweden
Daniel Tornero, University of Barcelona, Spain
Tristan Bouschet, INSERM U1191 Institut de Génomique Fonctionnelle (IGF), France  

Copyright: © 2019 Alia, Terrigno, Busti, Cremisi and Caleo. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: PhD. Claudia Alia, Institute of Neuroscience (CNR), Pisa, 56124, Tuscany, Italy, alia@in.cnr.it