Please use this identifier to cite or link to this item:
https://hdl.handle.net/10316/106103
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Barros, Inês | - |
dc.contributor.author | Marcelo, Adriana | - |
dc.contributor.author | Silva, Teresa P. | - |
dc.contributor.author | Barata, João | - |
dc.contributor.author | Ramos, António David Rufino | - |
dc.contributor.author | Almeida, Luís P. de | - |
dc.contributor.author | Miranda, Catarina O. | - |
dc.date.accessioned | 2023-03-21T08:56:16Z | - |
dc.date.available | 2023-03-21T08:56:16Z | - |
dc.date.issued | 2020 | - |
dc.identifier.issn | 1662-5102 | pt |
dc.identifier.uri | https://hdl.handle.net/10316/106103 | - |
dc.description.abstract | Polyglutamine (polyQ) diseases are a group of inherited neurodegenerative disorders caused by the expansion of the cytosine-adenine-guanine (CAG) repeat. This mutation encodes extended glutamine (Q) tract in the disease protein, resulting in the alteration of its conformation/physiological role and in the formation of toxic fragments/aggregates of the protein. This group of heterogeneous disorders shares common molecular mechanisms, which opens the possibility to develop a pan therapeutic approach. Vast efforts have been made to develop strategies to alleviate disease symptoms. Nonetheless, there is still no therapy that can cure or effectively delay disease progression of any of these disorders. Mesenchymal stromal cells (MSC) are promising tools for the treatment of polyQ disorders, promoting protection, tissue regeneration, and/or modulation of the immune system in animal models. Accordingly, data collected from clinical trials have so far demonstrated that transplantation of MSC is safe and delays the progression of some polyQ disorders for some time. However, to achieve sustained phenotypic amelioration in clinics, several treatments may be necessary. Therefore, efforts to develop new strategies to improve MSC's therapeutic outcomes have been emerging. In this review article, we discuss the current treatments and strategies used to reduce polyQ symptoms and major pre-clinical and clinical achievements obtained with MSC transplantation as well as remaining flaws that need to be overcome. The requirement to cross the blood-brain-barrier (BBB), together with a short rate of cell engraftment in the lesioned area and low survival of MSC in a pathophysiological context upon transplantation may contribute to the transient therapeutic effects. We also review methods like pre-conditioning or genetic engineering of MSC that can be used to increase MSC survival in vivo, cellular-free approaches-i.e., MSC-conditioned medium (CM) or MSC-derived extracellular vesicles (EVs) as a way of possibly replacing the use of MSC and methods required to standardize the potential of MSC/MSC-derived products. These are fundamental questions that need to be addressed to obtain maximum MSC performance in polyQ diseases and therefore increase clinical benefits. | pt |
dc.description.sponsorship | Our group is supported by the European Regional Development Fund through the Regional Operational Program Center2020, Competitiveness Factors Operational Program (COMPETE 2020), and National Funds through Foundation for Science and Technology (FCT): BrainHealth2020 projects (CENTRO- 01-0145-FEDER-000008), ViraVector (CENTRO-01-0145- FEDER-022095), CortaCAGs (POCI-01-0145-FEDER-016719), SpreadSilencing POCI-01-0145-FEDER-029716, Imagene POCI- 01-0145-FEDER-016807, CancelStem POCI-01-0145-FEDER- 016390, as well as UID4950/2020 (to CM), BIN—National Brain Imaging Network (CENTRO-01-0145-FEDER-022118) and the Association Française Contre les Myopathies—Téléthon no. 21163 and the SynSpread, European SCA3/MJD Initiative and ModelPolyQ under the EU Joint Program, the last two co-funded by the European Union H2020 program, GA No. 643417; by National Ataxia Foundation, the American Portuguese Biomedical Research Fund, and the Richard Chin and Lily Lock Machado-Joseph Disease Research Fund. IB was supported by FCT fellowship (SFRH/BD/148877/2019). | - |
dc.language.iso | eng | pt |
dc.publisher | Frontiers Media S.A. | pt |
dc.rights | openAccess | pt |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | pt |
dc.subject | mesenchymal stromal cells | pt |
dc.subject | polyglutamine disorders | pt |
dc.subject | neurodegenerative disorders | pt |
dc.subject | cell therapy | pt |
dc.subject | extracellular vesicles | pt |
dc.subject | secretome | pt |
dc.title | Mesenchymal Stromal Cells' Therapy for Polyglutamine Disorders: Where Do We Stand and Where Should We Go? | pt |
dc.type | article | - |
degois.publication.firstPage | 584277 | pt |
degois.publication.title | Frontiers in Cellular Neuroscience | pt |
dc.peerreviewed | yes | pt |
dc.identifier.doi | 10.3389/fncel.2020.584277 | pt |
degois.publication.volume | 14 | pt |
dc.date.embargo | 2020-01-01 | * |
uc.date.periodoEmbargo | 0 | pt |
item.openairetype | article | - |
item.fulltext | Com Texto completo | - |
item.languageiso639-1 | en | - |
item.grantfulltext | open | - |
item.cerifentitytype | Publications | - |
item.openairecristype | http://purl.org/coar/resource_type/c_18cf | - |
crisitem.author.dept | CNC - Center for Neuroscience and Cell Biology | - |
crisitem.author.researchunit | CNC - Center for Neuroscience and Cell Biology | - |
crisitem.author.researchunit | CNC - Center for Neuroscience and Cell Biology | - |
crisitem.author.researchunit | CNC - Center for Neuroscience and Cell Biology | - |
crisitem.author.researchunit | CIBB - Center for Innovative Biomedicine and Biotechnology | - |
crisitem.author.researchunit | CNC - Center for Neuroscience and Cell Biology | - |
crisitem.author.researchunit | CIBB - Center for Innovative Biomedicine and Biotechnology | - |
crisitem.author.researchunit | CNC - Center for Neuroscience and Cell Biology | - |
crisitem.author.orcid | 0000-0002-3893-6416 | - |
crisitem.author.orcid | 0000-0002-7327-0170 | - |
crisitem.author.orcid | 0000-0001-5831-3307 | - |
crisitem.author.orcid | 0000-0001-5241-8108 | - |
Appears in Collections: | I&D CNC - Artigos em Revistas Internacionais I&D CIBB - Artigos em Revistas Internacionais IIIUC - Artigos em Revistas Internacionais FFUC- Artigos em Revistas Internacionais |
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File | Description | Size | Format | |
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Mesenchymal Stromal Cells’ Therapy for Polyglutamine Disorders.pdf | 1.81 MB | Adobe PDF | View/Open |
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