Stem cell therapy is considered a promising approach in the treatment of amyotrophic lateral sclerosis (ALS) and mesenchymal stem cells (MSCs) seem to be the most effective in ALS animal models. The umbilical cord (UC) is a source of highly proliferating fetal MSCs, more easily collectable than other MSCs. Recently we demonstrated that human (h) UC-MSCs, double labeled with fluorescent nanoparticles and Hoechst-33258 and transplanted intracerebroventricularly (ICV) into SOD1G93A transgenic mice, partially migrated into the spinal cord after a single injection. This prompted us to assess the effect of repeated ICV injections of hUC-MSCs on disease progression in SOD1G93A mice. Although no transplanted cells migrated to the spinal cord, a partial but significant protection of motor neurons (MNs) was found in the lumbar spinal cord of hUC-MSCs-treated SOD1G93A mice, accompanied by a shift from a pro-inflammatory (IL-6, IL-1β) to anti-inflammatory (IL-4, IL-10) and neuroprotective (IGF-1) environment in the lumbar spinal cord, probably linked to the activation of p-Akt survival pathway in both motor neurons and reactive astrocytes. However, this treatment neither prevented the muscle denervation nor delayed the disease progression of mice, emphasizing the growing evidence that protecting the motor neuron perikarya is not sufficient to delay the ALS progression.

Multiple intracerebroventricular injections of human umbilical cord mesenchymal stem cells delay motor neurons loss but not disease progression of SOD1G93A mice / Sironi, F.; Vallarola, A.; Violatto, M. B.; Talamini, L.; Freschi, M.; De Gioia, R.; Capelli, C.; Agostini, A.; Moscatelli, D.; Tortarolo, M.; Bigini, P.; Introna, M.; Bendotti, C.. - In: STEM CELL RESEARCH. - ISSN 1873-5061. - 25:(2017), pp. 166-178. [10.1016/j.scr.2017.11.005]

Multiple intracerebroventricular injections of human umbilical cord mesenchymal stem cells delay motor neurons loss but not disease progression of SOD1G93A mice

Vallarola A.;
2017

Abstract

Stem cell therapy is considered a promising approach in the treatment of amyotrophic lateral sclerosis (ALS) and mesenchymal stem cells (MSCs) seem to be the most effective in ALS animal models. The umbilical cord (UC) is a source of highly proliferating fetal MSCs, more easily collectable than other MSCs. Recently we demonstrated that human (h) UC-MSCs, double labeled with fluorescent nanoparticles and Hoechst-33258 and transplanted intracerebroventricularly (ICV) into SOD1G93A transgenic mice, partially migrated into the spinal cord after a single injection. This prompted us to assess the effect of repeated ICV injections of hUC-MSCs on disease progression in SOD1G93A mice. Although no transplanted cells migrated to the spinal cord, a partial but significant protection of motor neurons (MNs) was found in the lumbar spinal cord of hUC-MSCs-treated SOD1G93A mice, accompanied by a shift from a pro-inflammatory (IL-6, IL-1β) to anti-inflammatory (IL-4, IL-10) and neuroprotective (IGF-1) environment in the lumbar spinal cord, probably linked to the activation of p-Akt survival pathway in both motor neurons and reactive astrocytes. However, this treatment neither prevented the muscle denervation nor delayed the disease progression of mice, emphasizing the growing evidence that protecting the motor neuron perikarya is not sufficient to delay the ALS progression.
25
166
178
Multiple intracerebroventricular injections of human umbilical cord mesenchymal stem cells delay motor neurons loss but not disease progression of SOD1G93A mice / Sironi, F.; Vallarola, A.; Violatto, M. B.; Talamini, L.; Freschi, M.; De Gioia, R.; Capelli, C.; Agostini, A.; Moscatelli, D.; Tortarolo, M.; Bigini, P.; Introna, M.; Bendotti, C.. - In: STEM CELL RESEARCH. - ISSN 1873-5061. - 25:(2017), pp. 166-178. [10.1016/j.scr.2017.11.005]
Sironi, F.; Vallarola, A.; Violatto, M. B.; Talamini, L.; Freschi, M.; De Gioia, R.; Capelli, C.; Agostini, A.; Moscatelli, D.; Tortarolo, M.; Bigini, P.; Introna, M.; Bendotti, C.
File in questo prodotto:
File Dimensione Formato  
Sironi et al SCR 2017.pdf

accesso aperto

Tipologia: Versione dell'editore (versione pubblicata)
Dimensione 4.28 MB
Formato Adobe PDF
4.28 MB Adobe PDF Visualizza/Apri
Pubblicazioni consigliate

Caricamento pubblicazioni consigliate

Licenza Creative Commons
I metadati presenti in IRIS UNIMORE sono rilasciati con licenza Creative Commons CC0 1.0 Universal, mentre i file delle pubblicazioni sono rilasciati con licenza Attribuzione 4.0 Internazionale (CC BY 4.0), salvo diversa indicazione.
In caso di violazione di copyright, contattare Supporto Iris

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11380/1202114
Citazioni
  • ???jsp.display-item.citation.pmc??? 10
  • Scopus 19
  • ???jsp.display-item.citation.isi??? 18
social impact