Combined intramuscular and intraspinal transplant of bone marrow cells improves neuromuscular function in the SOD1G93A mice

Martínez-Muriana, A. ; Pastor, D. ; Mancuso, R. ; Rando, A. ; Osta, R. (Universidad de Zaragoza) ; Martínez, S. ; López-Vales, R. ; Navarro, X.

Resumen: Background: 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. Methods: Since ALS begins with a distal axonopathy, in a first assay, we performed injection of bone marrow cells into two hindlimb muscles of transgenic SOD1G93A 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. Results: 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. Conclusion: 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.

Idioma: Inglés

DOI: 10.1186/s13287-020-1573-6

Año: 2020

Publicado en: Stem cell research & therapy 11, 1 (2020), [11 pp.]
ISSN: 1757-6512

Originalmente disponible en: Texto completo de la revista

Factor impacto JCR: 6.832 (2020)

Categ. JCR: CELL BIOLOGY rank: 45 / 195 = 0.231 (2020) - Q1 - T1
Categ. JCR: CELL & TISSUE ENGINEERING rank: 7 / 29 = 0.241 (2020) - Q1 - T1
Categ. JCR: MEDICINE, RESEARCH & EXPERIMENTAL rank: 24 / 140 = 0.171 (2020) - Q1 - T1

Factor impacto SCIMAGO: 1.599 - Biochemistry, Genetics and Molecular Biology (miscellaneous) (Q1) - Molecular Medicine (Q1) - Medicine (miscellaneous) (Q1) - Cell Biology (Q1)

Financiación: info:eu-repo/grantAgreement/ES/MINECO/SEV-2013-0317

Tipo y forma: Artículo (Versión definitiva)

Área (Departamento): Área Genética (Dpto. Anatom.,Embri.Genét.Ani.)