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Barros I, Marcelo A, Silva TP, et al. Mesenchymal Stromal Cells' Therapy for Polyglutamine Disorders: Where Do We Stand and Where Should We Go?. Front Cell Neurosci. 2020;14:584277doi: 10.3389/fncel.2020.584277.
Barros, I., Marcelo, A., Silva, T. P., Barata, J., Rufino-Ramos, D., Pereira de Almeida, L., & Miranda, C. O. (2020). Mesenchymal Stromal Cells' Therapy for Polyglutamine Disorders: Where Do We Stand and Where Should We Go?. Frontiers in cellular neuroscience, 14584277. https://doi.org/10.3389/fncel.2020.584277
Barros, Inês, et al. "Mesenchymal Stromal Cells' Therapy for Polyglutamine Disorders: Where Do We Stand and Where Should We Go?." Frontiers in cellular neuroscience vol. 14 (2020): 584277. doi: https://doi.org/10.3389/fncel.2020.584277
Barros I, Marcelo A, Silva TP, Barata J, Rufino-Ramos D, Pereira de Almeida L, Miranda CO. Mesenchymal Stromal Cells' Therapy for Polyglutamine Disorders: Where Do We Stand and Where Should We Go?. Front Cell Neurosci. 2020 Oct 06;14:584277. doi: 10.3389/fncel.2020.584277. eCollection 2020. PMID: 33132851; PMCID: PMC7573388.
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Front Cell Neurosci. 2020 Oct 06;14:584277. doi: 10.3389/fncel.2020.584277. eCollection 2020.

Mesenchymal Stromal Cells' Therapy for Polyglutamine Disorders: Where Do We Stand and Where Should We Go?.

Frontiers in cellular neuroscience

Inês Barros, Adriana Marcelo, Teresa P Silva, João Barata, David Rufino-Ramos, Luís Pereira de Almeida, Catarina O Miranda

Affiliations

  1. CNC-Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.
  2. CIBB-Center for Innovative Biomedicine and Biotechnology, University of Coimbra, Coimbra, Portugal.
  3. III-Institute for Interdisciplinary Research, University of Coimbra, Coimbra, Portugal.
  4. Faculty of Pharmacy, University of Coimbra, Coimbra, Portugal.
  5. Viravector-Viral Vector for Gene Transfer Core Facility, University of Coimbra, Coimbra, Portugal.

PMID: 33132851 PMCID: PMC7573388 DOI: 10.3389/fncel.2020.584277

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

Copyright © 2020 Barros, Marcelo, Silva, Barata, Rufino-Ramos, Pereira de Almeida and Miranda.

Keywords: cell therapy; extracellular vesicles; mesenchymal stromal cells; neurodegenerative disorders; polyglutamine disorders; secretome

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