Universität zu Köln

Barros, Ines, Marcelo, Adriana, Silva, Teresa P. ORCID: 0000-0002-5039-703X, Barata, Joao, Rufino-Ramos, David, Pereira de Almeida, Luis ORCID: 0000-0001-5831-3307 and Miranda, Catarina O. (2020). Mesenchymal Stromal Cells' Therapy for Polyglutamine Disorders: Where Do We Stand and Where Should We Go? Front. Cell. Neurosci., 14. LAUSANNE: FRONTIERS MEDIA SA. ISSN 1662-5102

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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 survivalin 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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Barros, Ines UNSPECIFIED UNSPECIFIED UNSPECIFIED Marcelo, Adriana UNSPECIFIED UNSPECIFIED UNSPECIFIED Silva, Teresa P. UNSPECIFIED orcid.org/0000-0002-5039-703X UNSPECIFIED Barata, Joao UNSPECIFIED UNSPECIFIED UNSPECIFIED Rufino-Ramos, David UNSPECIFIED UNSPECIFIED UNSPECIFIED Pereira de Almeida, Luis UNSPECIFIED orcid.org/0000-0001-5831-3307 UNSPECIFIED Miranda, Catarina O. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-315625
DOI:	10.3389/fncel.2020.584277
Journal or Publication Title:	Front. Cell. Neurosci.
Volume:	14
Date:	2020
Publisher:	FRONTIERS MEDIA SA
Place of Publication:	LAUSANNE
ISSN:	1662-5102
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language MACHADO-JOSEPH-DISEASE; MOOD STABILIZERS LITHIUM; STEM-CELLS; BONE-MARROW; SPINOCEREBELLAR ATAXIA; HUNTINGTONS-DISEASE; MOUSE MODEL; RAT MODEL; EXTRACELLULAR VESICLES; VALPROIC ACID Multiple languages Neurosciences Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/31562