title: Distribution of mesenchymal stem cells and effects on neuronal survival and axon regeneration after optic nerve crush and cell therapy.
abstract: Bone marrow-derived cells have been used in different animal models of neurological diseases. We investigated the therapeutic potential of mesenchymal stem cells (MSC) injected into the vitreous body in a model of optic nerve injury. Adult (3-5 months old) Lister Hooded rats underwent unilateral optic nerve crush followed by injection of MSC or the vehicle into the vitreous body. Before they were injected, MSC were labeled with a fluorescent dye or with superparamagnetic iron oxide nanoparticles, which allowed us to track the cells in vivo by magnetic resonance imaging. Sixteen and 28 days after injury, the survival of retinal ganglion cells was evaluated by assessing the number of Tuj1- or Brn3a-positive cells in flat-mounted retinas, and optic nerve regeneration was investigated after anterograde labeling of the optic axons with cholera toxin B conjugated to Alexa 488. Transplanted MSC remained in the vitreous body and were found in the eye for several weeks. Cell therapy significantly increased the number of Tuj1- and Brn3a-positive cells in the retina and the number of axons distal to the crush site at 16 and 28 days after optic nerve crush, although the RGC number decreased over time. MSC therapy was associated with an increase in the FGF-2 expression in the retinal ganglion cells layer, suggesting a beneficial outcome mediated by trophic factors. Interleukin-1β expression was also increased by MSC transplantation. In summary, MSC protected RGC and stimulated axon regeneration after optic nerve crush. The long period when the transplanted cells remained in the eye may account for the effect observed. However, further studies are needed to overcome eventually undesirable consequences of MSC transplantation and to potentiate the beneficial ones in order to sustain the neuroprotective effect overtime.
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil; Instituto Nacional de Ciência e Tecnologia de Biologia Estrutural e Bioimagem, INBEB, Rio de Janeiro, Brazil.
authors.forename: Louise Alessandra
authors.initials: LA
authors.lastname: Mesentier-Louro
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil; Instituto Nacional de Ciência e Tecnologia de Biologia Estrutural e Bioimagem, INBEB, Rio de Janeiro, Brazil.
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, Brazil; Instituto Nacional de Ciência e Tecnologia de Biologia Estrutural e Bioimagem, INBEB, Rio de Janeiro, Brazil.
authors.forename: Almir Jordão
authors.initials: AJ
authors.lastname: da Silva-Junior
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil; Instituto Nacional de Ciência e Tecnologia de Biologia Estrutural e Bioimagem, INBEB, Rio de Janeiro, Brazil.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Nascimento-Dos-Santos
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil; Instituto Nacional de Ciência e Tecnologia de Biologia Estrutural e Bioimagem, INBEB, Rio de Janeiro, 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, Brazil; Instituto Nacional de Ciência e Tecnologia de Biologia Estrutural e Bioimagem, INBEB, Rio de Janeiro, Brazil.
authors.forename: Ana Beatriz Padilha
authors.initials: AB
authors.lastname: de Figueirêdo
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil; Instituto Nacional de Ciência e Tecnologia de Biologia Estrutural e Bioimagem, INBEB, Rio de Janeiro, Brazil.
authors.forename: Ana Luiza
authors.initials: AL
authors.lastname: Torres
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil; Instituto Nacional de Ciência e Tecnologia de Biologia Estrutural e Bioimagem, INBEB, Rio de Janeiro, Brazil.
authors.forename: Bruno D
authors.initials: BD
authors.lastname: Paredes
authors.affiliation: National Center of Structural Biology and Bioimaging (CENABIO), Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Camila
authors.initials: C
authors.lastname: Teixeira
authors.affiliation: National Center of Structural Biology and Bioimaging (CENABIO), Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil; D'Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil; Institute of Biomedical Sciences (ICB), Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Fernanda
authors.initials: F
authors.lastname: Tovar-Moll
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil; Instituto Nacional de Ciência e Tecnologia de Biologia Estrutural e Bioimagem, INBEB, Rio de Janeiro, 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, Brazil; Instituto Nacional de Ciência e Tecnologia de Biologia Estrutural e Bioimagem, INBEB, Rio de Janeiro, Brazil.
authors.forename: Marcelo F
authors.initials: MF
authors.lastname: Santiago
mesh_terms: D017667:Adipocytes / Q000166:cytology; D000818:Animals; D000954:Antigens, Surface / Q000378:metabolism; D001369:Axons / Q000378:metabolism*; D002454:Cell Differentiation; D002470:Cell Survival; D064987:Cell- and Tissue-Based Therapy; D019902:Chondrocytes / Q000166:cytology; D004195:Disease Models, Animal; D016222:Fibroblast Growth Factor 2 / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D016130:Immunophenotyping; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D009409:Nerve Crush; D009416:Nerve Regeneration; D009474:Neurons / Q000378:metabolism*; D009900:Optic Nerve; D020221:Optic Nerve Injuries / Q000175:diagnosis / Q000378:metabolism* / Q000628:therapy*; D010011:Osteocytes / Q000166:cytology; D051381:Rats; D012165:Retinal Ganglion Cells / Q000378:metabolism
chemical_list: D000954:Antigens, Surface; D053583:Interleukin-1beta; D016222:Fibroblast Growth Factor 2