title: Sustained effect of bone marrow mononuclear cell therapy in axonal regeneration in a model of optic nerve crush.
abstract: In adult mammals, the regeneration of the optic nerve is very limited and at the moment there are several groups trying different approaches to increase retinal ganglion cell (RGC) survival and axonal outgrowth. One promising approach is cell therapy. In previous work, we performed intravitreal transplantation of bone-marrow mononuclear cells (BMMCs) after optic nerve crush in adult rats and we demonstrated an increase in RGC survival and axon outgrowth 14 days after injury. In the present work, we investigated if these results could be sustained for a longer period of time. Optic nerve crush was performed in Lister-hooded adult rats and BMMC or saline injections were performed shortly after injury. Neuronal survival and regeneration were evaluated in rats׳ retina and optic nerve after 28 days. We demonstrated an increase of 5.2 fold in the axon outgrowth 28 days after lesion, but the BMMCs had no effect on RGC survival. In an attempt to prolong RGC survival, we established a new protocol with two BMMC injections, the second one 7 days after the injury. Untreated animals received two injections of saline. We observed that although the axonal outgrowth was still increased after the second BMMC injection, the RGC survival was not significantly different from untreated animals. These results demonstrate that BMMCs transplantation promotes neuroregeneration at least until 28 days after injury. However, the effects on RGC survival previously observed by us at 14 days were not sustained at 28 days and could not be prolonged with a second dose of BMMC.
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho; Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, 21941-902, Brazil; Instituto Nacional de Ciência e Tecnologia de Biologia Estrutural e Bioimagem-INBEB; Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, 21941-902, Brazil. Electronic address: camilazv@biof.ufrj.br.
authors.forename: Camila
authors.initials: C
authors.lastname: Zaverucha-do-Valle
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho; Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, 21941-902, Brazil; Instituto Nacional de Ciência e Tecnologia de Biologia Estrutural e Bioimagem-INBEB; Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, 21941-902, Brazil.
authors.forename: Louise
authors.initials: L
authors.lastname: Mesentier-Louro
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho; Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, 21941-902, Brazil; Instituto Nacional de Ciência e Tecnologia de Biologia Estrutural e Bioimagem-INBEB; Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, 21941-902, Brazil.
authors.forename: Fernanda
authors.initials: F
authors.lastname: Gubert
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho; Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, 21941-902, Brazil; Instituto Nacional de Ciência e Tecnologia de Biologia Estrutural e Bioimagem-INBEB; Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, 21941-902, Brazil.
authors.forename: Nicoli
authors.initials: N
authors.lastname: Mortari
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho; Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, 21941-902, Brazil; Instituto Nacional de Ciência e Tecnologia de Biologia Estrutural e Bioimagem-INBEB; Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, 21941-902, Brazil.
authors.forename: Ana Beatriz
authors.initials: AB
authors.lastname: Padilha
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho; Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, 21941-902, Brazil; Instituto Nacional de Ciência e Tecnologia de Biologia Estrutural e Bioimagem-INBEB; Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, 21941-902, Brazil.
authors.forename: Bruno D
authors.initials: BD
authors.lastname: Paredes
authors.affiliation: Laboratório de Células-Tronco, Centro Nacional de Transplante de Medula Óssea, Instituto Nacional de Câncer, Rio de Janeiro, Brazil; Universidade do Estado do Rio de Janeiro, Instituto de Biologia Roberto Alcantara Gomes, Departamento de Biofísica e Biometria, Rio de Janeiro, Brazil.
authors.forename: Andre
authors.initials: A
authors.lastname: Mencalha
authors.affiliation: Laboratório de Células-Tronco, Centro Nacional de Transplante de Medula Óssea, Instituto Nacional de Câncer, Rio de Janeiro, Brazil.
authors.forename: Eliana
authors.initials: E
authors.lastname: Abdelhay
authors.affiliation: Instituto Nacional de Ciência e Tecnologia de Biologia Estrutural e Bioimagem-INBEB; Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, 21941-902, Brazil.
authors.forename: Camila
authors.initials: C
authors.lastname: Teixeira
authors.affiliation: Instituto Nacional de Ciência e Tecnologia de Biologia Estrutural e Bioimagem-INBEB; Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, 21941-902, Brazil; Instituto D'Or de Pesquisa e Educação (IDOR), Rio de Janeiro, Brazil.
authors.forename: Fernanda G M
authors.initials: FG
authors.lastname: Ferreira
authors.affiliation: Instituto Nacional de Ciência e Tecnologia de Biologia Estrutural e Bioimagem-INBEB; Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, 21941-902, Brazil; Instituto D'Or de Pesquisa e Educação (IDOR), Rio de Janeiro, Brazil; Instituto de Ciência Biomédicas; Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, 21941-902, Brazil.
authors.forename: Fernanda
authors.initials: F
authors.lastname: Tovar-Moll
authors.affiliation: Instituto Nacional de Ciência e Tecnologia de Biologia Estrutural e Bioimagem-INBEB; Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, 21941-902, Brazil; Departamento de Radiologia, Faculdade de Medicina, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Sergio Augusto L
authors.initials: SA
authors.lastname: de Souza
authors.affiliation: Departamento de Radiologia, Faculdade de Medicina, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Bianca
authors.initials: B
authors.lastname: Gutfilen
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho; Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, 21941-902, Brazil; Instituto Nacional de Ciência e Tecnologia de Biologia Estrutural e Bioimagem-INBEB; Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, 21941-902, Brazil.
authors.forename: Rosalia
authors.initials: R
authors.lastname: Mendez-Otero
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho; Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, 21941-902, Brazil; Instituto Nacional de Ciência e Tecnologia de Biologia Estrutural e Bioimagem-INBEB; Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, 21941-902, Brazil.
authors.forename: Marcelo F
authors.initials: MF
authors.lastname: Santiago
mesh_terms: D000818:Animals; D001370:Axonal Transport; D001369:Axons / Q000502:physiology*; D016026:Bone Marrow Transplantation; D002470:Cell Survival; D005136:Eye Proteins / Q000096:biosynthesis / Q000235:genetics; D020869:Gene Expression Profiling; D006085:Graft Survival; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis / Q000235:genetics; D009409:Nerve Crush; D009416:Nerve Regeneration; D020221:Optic Nerve Injuries / Q000503:physiopathology / Q000628:therapy*; D051381:Rats; D012165:Retinal Ganglion Cells / Q000473:pathology
chemical_list: D005136:Eye Proteins; D036341:Intercellular Signaling Peptides and Proteins
keywords: Axonal regeneration; Bone marrow mononuclear cell; Cell therapy; Optic nerve; Retinal ganglion cell survival