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Title: Successes and Hurdles in Stem Cells Application and Production for Brain Transplantation
Authors: Henrique, Daniel 
Moreira, Ricardo 
Schwamborn, Jens
Almeida, Luís Pereira de 
Mendonça, Liliana 
Keywords: stem cells transplantation; brain; neuronal integration and survival; adult brain plasticity; regulatory framework
Issue Date: 2019
Publisher: Frontiers Media S.A.
Project: This work was supported by the European Union through the Regional Operational Program CENTRO2020, the Competitiveness Factors Operational Program (COMPETE 2020), and the National Funds through FCT (Foundation for Science and Technology) – projects Brain Health 2020 (CENTRO-01-0145-FEDER-000008), POCI-01-0145-FEDER- 016719, POCI-01-0145-FEDER-029716, and PTDC/BTMORG/ 30737/2017 (POCI-01-0145-FEDER-030737). This work was also funded by the National Ataxia Foundation, the French Muscular Dystrophy Association (AFM-Téléthon), Trampoline Grant #20126, SynSpread, Model PolyQ and ESMI: under the EU Joint Program – Neurodegenerative Disease Research (JPND), and the Richard Chin and Lily Lock Machado-Joseph Disease Research Fund. 
Serial title, monograph or event: Frontiers in Neuroscience
Volume: 13
Abstract: Brain regenerative strategies through the transplantation of stem cells hold the potential to promote functional rescue of brain lesions caused either by trauma or neurodegenerative diseases. Most of the positive modulations fostered by stem cells are fueled by bystander effects, namely increase of neurotrophic factors levels and reduction of neuroinflammation. Nevertheless, the ultimate goal of cell therapies is to promote cell replacement. Therefore, the ability of stem cells to migrate and differentiate into neurons that later become integrated into the host neuronal network replacing the lost neurons has also been largely explored. However, as most of the preclinical studies demonstrate, there is a small functional integration of graft-derived neurons into host neuronal circuits. Thus, it is mandatory to better study the whole brain cell therapy approach in order to understand what should be better comprehended concerning graft-derived neuronal and glial cells migration and integration before we can expect these therapies to be ready as a viable solution for brain disorder treatment. Therefore, this review discusses the positive mechanisms triggered by cell transplantation into the brain, the limitations of adult brain plasticity that might interfere with the neuroregeneration process, as well as some strategies tested to overcome some of these limitations. It also considers the efforts that have been made by the regulatory authorities to lead to better standardization of preclinical and clinical studies in this field in order to reduce the heterogeneity of the obtained results.
ISSN: 1662-4548
DOI: 10.3389/fnins.2019.01194
Rights: openAccess
Appears in Collections:I&D CNC - Artigos em Revistas Internacionais
I&D CIBB - Artigos em Revistas Internacionais
FFUC- Artigos em Revistas Internacionais

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