Survival and Neuronal Differentiation of Mesenchymal Stem Cells Transplanted into the Rodent Brain Are Dependent upon Microenvironment
Contribuinte(s) |
UNIVERSIDADE DE SÃO PAULO |
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Data(s) |
18/04/2012
18/04/2012
2010
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Resumo |
Introduction: The successful integration of stem cells in adult brain has become a central issue in modern neuroscience. In this study we sought to test the hypothesis that survival and neurodifferentiation of mesenchymal stem cells (MSCs) may be dependent upon microenvironmental conditions according to the site of implant in the brain. Methods: MSCs were isolated from adult rats and labeled with enhanced-green fluorescent protein (eGFP) lentivirus. A cell suspension was implanted stereotactically into the brain of 50 young rats, into one neurogenic area (hippocampus), and into another nonneurogenic area (striatum). Animals were sacrificed 6 or 12 weeks after surgery, and brains were stained for mature neuronal markers. Cells coexpressing NeuN (neuronal specific nuclear protein) and GFP (green fluorescent protein) were counted stereologically at both targets. Results: The isolated cell population was able to generate neurons positive for microtubule-associated protein 2 (MAP2), neuronal-specific nuclear protein (NeuN), and neurofilament 200 (NF200) in vitro. Electrophysiology confirmed expression of voltage-gated ionic channels. Once implanted into the hippocampus, cells survived for up to 12 weeks, migrated away from the graft, and gave rise to mature neurons able to synthesize neurotransmitters. By contrast, massive cell degeneration was seen in the striatum, with no significant migration. Induction of neuronal differentiation with increased cyclic adenosine monophosphate in the culture medium before implantation favored differentiation in vivo. Conclusions: Our data demonstrated that survival and differentiation of MSCs is strongly dependent upon a permissive microenvironment. Identification of the pro-neurogenic factors present in the hippocampus could subsequently allow for the integration of stem cells into nonpermissive areas of the central nervous system. DFG - Deutsche Forschungsgemeinschaft (DAAD) Deutscher Akademischer Austausch Dienst, Germany German Parkinson Foundation BMBF - Bundesministerium fur Bildung und Forschung, Germany |
Identificador |
TISSUE ENGINEERING PART A, v.16, n.9, p.2769-2782, 2010 1937-3341 http://producao.usp.br/handle/BDPI/15171 10.1089/ten.tea.2009.0686 |
Idioma(s) |
eng |
Publicador |
MARY ANN LIEBERT INC |
Relação |
Tissue Engineering Part A |
Direitos |
closedAccess Copyright MARY ANN LIEBERT INC |
Palavras-Chave | #MARROW STROMAL CELLS #UMBILICAL-CORD BLOOD #RAT PARKINSON-MODEL #BONE-MARROW #SPINAL-CORD #IN-VITRO #HIPPOCAMPAL NEUROGENESIS #FUNCTIONAL RECOVERY #ADULT NEUROGENESIS #INDUCTION #Cell & Tissue Engineering #Biotechnology & Applied Microbiology #Cell Biology |
Tipo |
article original article publishedVersion |