Combined intramuscular and intraspinal transplant of bone marrow cells improves neuromuscular function in the SOD1 G93A mice

The simultaneous contribution of several etiopathogenic disturbances makes amyotrophic lateral sclerosis (ALS) a fatal and challenging disease. Here, we studied two different cell therapy protocols to protect both central and peripheral nervous system in a murine model of ALS. Since ALS begins with...

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Autores: Martínez Muriana, Anna|||0000-0002-8645-1317, Pastor, Diego|||0000-0002-2884-6580, Mancuso, Renzo, Rando, Amaya, Osta, Rosario|||0000-0001-5687-6704, Martínez, Salvador, López Vales, Rubèn, Navarro, X. (Xavier)|||0000-0001-9849-902X
Tipo de recurso: artículo
Fecha de publicación:2020
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:226251
Acceso en línea:https://ddd.uab.cat/record/226251
https://dx.doi.org/urn:doi:10.1186/s13287-020-1573-6
Access Level:acceso abierto
Palabra clave:ALS
SOD1
Bone marrow
Stem cells
Motoneuron disease
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spelling Combined intramuscular and intraspinal transplant of bone marrow cells improves neuromuscular function in the SOD1 G93A miceMartínez Muriana, Anna|||0000-0002-8645-1317Pastor, Diego|||0000-0002-2884-6580Mancuso, RenzoRando, AmayaOsta, Rosario|||0000-0001-5687-6704Martínez, SalvadorLópez Vales, RubènNavarro, X. (Xavier)|||0000-0001-9849-902XALSSOD1Bone marrowStem cellsMotoneuron diseaseThe simultaneous contribution of several etiopathogenic disturbances makes amyotrophic lateral sclerosis (ALS) a fatal and challenging disease. Here, we studied two different cell therapy protocols to protect both central and peripheral nervous system in a murine model of ALS. Since ALS begins with a distal axonopathy, in a first assay, we performed injection of bone marrow cells into two hindlimb muscles of transgenic SOD1 G93A mice. In a second study, we combined intramuscular and intraspinal injection of bone marrow cells. Fluorescence-activated cell sorting was used to assess the survival of the transplanted cells into the injected tissues. The mice were assessed from 8 to 16 weeks of age by means of locomotion and electrophysiological tests. After follow-up, the spinal cord was processed for analysis of motoneuron survival and glial cell reactivity. We found that, after intramuscular injection, bone marrow cells were able to engraft within the muscle. However, bone marrow cell intramuscular injection failed to promote a general therapeutic effect. In the second approach, we found that bone marrow cells had limited survival in the spinal cord, but this strategy significantly improved motor outcomes. Moreover, we also found that the dual cell therapy tended to preserve spinal motoneurons at late stages of the disease and to reduce microgliosis, although this did not prolong mice survival. Overall, our findings suggest that targeting more than one affected area of the motor system at once with bone marrow cell therapy results in a valuable therapeutic intervention for ALS. 22020-01-0120202020-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/226251https://dx.doi.org/urn:doi:10.1186/s13287-020-1573-6reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengMinisterio de Economía y Competitividad https://doi.org/10.13039/501100003329 SEV-2013-0317open accesshttp://purl.org/coar/access_right/c_abf2Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:2262512026-06-06T12:50:31Z
dc.title.none.fl_str_mv Combined intramuscular and intraspinal transplant of bone marrow cells improves neuromuscular function in the SOD1 G93A mice
title Combined intramuscular and intraspinal transplant of bone marrow cells improves neuromuscular function in the SOD1 G93A mice
spellingShingle Combined intramuscular and intraspinal transplant of bone marrow cells improves neuromuscular function in the SOD1 G93A mice
Martínez Muriana, Anna|||0000-0002-8645-1317
ALS
SOD1
Bone marrow
Stem cells
Motoneuron disease
title_short Combined intramuscular and intraspinal transplant of bone marrow cells improves neuromuscular function in the SOD1 G93A mice
title_full Combined intramuscular and intraspinal transplant of bone marrow cells improves neuromuscular function in the SOD1 G93A mice
title_fullStr Combined intramuscular and intraspinal transplant of bone marrow cells improves neuromuscular function in the SOD1 G93A mice
title_full_unstemmed Combined intramuscular and intraspinal transplant of bone marrow cells improves neuromuscular function in the SOD1 G93A mice
title_sort Combined intramuscular and intraspinal transplant of bone marrow cells improves neuromuscular function in the SOD1 G93A mice
dc.creator.none.fl_str_mv Martínez Muriana, Anna|||0000-0002-8645-1317
Pastor, Diego|||0000-0002-2884-6580
Mancuso, Renzo
Rando, Amaya
Osta, Rosario|||0000-0001-5687-6704
Martínez, Salvador
López Vales, Rubèn
Navarro, X. (Xavier)|||0000-0001-9849-902X
author Martínez Muriana, Anna|||0000-0002-8645-1317
author_facet Martínez Muriana, Anna|||0000-0002-8645-1317
Pastor, Diego|||0000-0002-2884-6580
Mancuso, Renzo
Rando, Amaya
Osta, Rosario|||0000-0001-5687-6704
Martínez, Salvador
López Vales, Rubèn
Navarro, X. (Xavier)|||0000-0001-9849-902X
author_role author
author2 Pastor, Diego|||0000-0002-2884-6580
Mancuso, Renzo
Rando, Amaya
Osta, Rosario|||0000-0001-5687-6704
Martínez, Salvador
López Vales, Rubèn
Navarro, X. (Xavier)|||0000-0001-9849-902X
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv ALS
SOD1
Bone marrow
Stem cells
Motoneuron disease
topic ALS
SOD1
Bone marrow
Stem cells
Motoneuron disease
description The simultaneous contribution of several etiopathogenic disturbances makes amyotrophic lateral sclerosis (ALS) a fatal and challenging disease. Here, we studied two different cell therapy protocols to protect both central and peripheral nervous system in a murine model of ALS. Since ALS begins with a distal axonopathy, in a first assay, we performed injection of bone marrow cells into two hindlimb muscles of transgenic SOD1 G93A mice. In a second study, we combined intramuscular and intraspinal injection of bone marrow cells. Fluorescence-activated cell sorting was used to assess the survival of the transplanted cells into the injected tissues. The mice were assessed from 8 to 16 weeks of age by means of locomotion and electrophysiological tests. After follow-up, the spinal cord was processed for analysis of motoneuron survival and glial cell reactivity. We found that, after intramuscular injection, bone marrow cells were able to engraft within the muscle. However, bone marrow cell intramuscular injection failed to promote a general therapeutic effect. In the second approach, we found that bone marrow cells had limited survival in the spinal cord, but this strategy significantly improved motor outcomes. Moreover, we also found that the dual cell therapy tended to preserve spinal motoneurons at late stages of the disease and to reduce microgliosis, although this did not prolong mice survival. Overall, our findings suggest that targeting more than one affected area of the motor system at once with bone marrow cell therapy results in a valuable therapeutic intervention for ALS.
publishDate 2020
dc.date.none.fl_str_mv 2
2020-01-01
2020
2020-01-01
dc.type.none.fl_str_mv Article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://ddd.uab.cat/record/226251
https://dx.doi.org/urn:doi:10.1186/s13287-020-1573-6
url https://ddd.uab.cat/record/226251
https://dx.doi.org/urn:doi:10.1186/s13287-020-1573-6
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 SEV-2013-0317
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Dipòsit Digital de Documents de la UAB
instname:Universitat Autònoma de Barcelona
instname_str Universitat Autònoma de Barcelona
reponame_str Dipòsit Digital de Documents de la UAB
collection Dipòsit Digital de Documents de la UAB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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