title: Bone marrow transplantation in hindlimb muscles of motoneuron degenerative mice reduces neuronal death and improves motor function.
abstract: Bone marrow has proved to be an adequate source of stem cells for the treatment of numerous disorders, including neurodegenerative diseases. Bone marrow can be easily and relatively painlessly extracted from a patient or allogenic donor and then transplanted into the degenerative area. Here, the grafted cells will activate a number of mechanisms in order to protect, repair, and/or regenerate the damaged tissue. These properties make the bone marrow a feasible source for cell therapy. In this work, we transplanted bone marrow cells into a mouse model of motoneuron degeneration, with the particularity of placing the cells in the hindlimb muscles rather than in the spinal cord where neuronal degeneration occurs. To this end, we analyze the possibility for the transplanted cells to increase the survival rate of the spinal cord motoneurons by axonal-guided retrograde neurotrophism. As a result, the mice significantly improved their motor functions. This coincided with an increased number of motoneurons innervating the treated muscle compared with the neurons innervating the non-treated contralateral symmetric muscle. In addition, we detected an increase in glial-derived neurotrophic factor in the spinal cord, a neurotrophic factor known to be involved in the rescue of degenerating motoneurons, exerting a neuroprotective effect. Thus, we have proved that bone marrow injected into the muscles is capable of rescuing these motoneurons from death, which may be a possible therapeutic approach for spinal cord motoneuron degenerative diseases, such as amyotrophic lateral sclerosis.
authors.affiliation: Sports Science Research Center, Miguel Hernández University, Elche, Alicante 03202, Spain. dpastor@umh.es
authors.forename: Diego
authors.initials: D
authors.lastname: Pastor
authors.forename: Mari Carmen
authors.initials: MC
authors.lastname: Viso-León
authors.forename: Arancha
authors.initials: A
authors.lastname: Botella-López
authors.forename: Jesus
authors.initials: J
authors.lastname: Jaramillo-Merchan
authors.forename: Jose M
authors.initials: JM
authors.lastname: Moraleda
authors.forename: Jonathan
authors.initials: J
authors.lastname: Jones
authors.forename: Salvador
authors.initials: S
authors.lastname: Martínez
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism; D016026:Bone Marrow Transplantation; D002470:Cell Survival; D064987:Cell- and Tissue-Based Therapy; D004195:Disease Models, Animal; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000235:genetics; D006614:Hindlimb / Q000601:surgery; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009046:Motor Neurons / Q000502:physiology; D018482:Muscle, Skeletal / Q000294:innervation* / Q000378:metabolism*; D009410:Nerve Degeneration / Q000378:metabolism / Q000628:therapy; D019636:Neurodegenerative Diseases / Q000628:therapy*; D020127:Recovery of Function; D013116:Spinal Cord / Q000166:cytology / Q000378:metabolism*
chemical_list: D051100:Glial Cell Line-Derived Neurotrophic Factor; D049452:Green Fluorescent Proteins