Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2010-6-23
pubmed:abstractText
Mesenchymal stromal cell (MSC) therapy has shown promise for the treatment of traumatic brain injury (TBI). Although the mechanism(s) by which MSCs offer protection is unclear, initial in vivo work has suggested that modulation of the locoregional inflammatory response could explain the observed benefit. We hypothesize that the direct implantation of MSCs into the injured brain activates resident neuronal stem cell (NSC) niches altering the intracerebral milieu. To test our hypothesis, we conducted initial in vivo studies, followed by a sequence of in vitro studies. In vivo: Sprague-Dawley rats received a controlled cortical impact (CCI) injury with implantation of 1 million MSCs 6 h after injury. Brain tissue supernatant was harvested for analysis of the proinflammatory cytokine profile. In vitro: NSCs were transfected with a firefly luciferase reporter for NFkappaB and placed in contact culture and transwell culture. Additionally, multiplex, quantitative PCR, caspase 3, and EDU assays were completed to evaluate NSC cytokine production, apoptosis, and proliferation, respectively. In vivo: Brain supernatant analysis showed an increase in the proinflammatory cytokines IL-1alpha, IL-1beta, and IL-6. In vitro: NSC NFkappaB activity increased only when in contact culture with MSCs. When in contact with MSCs, NSCs show an increase in IL-6 production as well as a decrease in apoptosis. Direct implantation of MSCs enhances neuroprotection via activation of resident NSC NFkappaB activity (independent of PI3 kinase/AKT pathway) leading to an increase in IL-6 production and decrease in apoptosis. In addition, the observed NFkappaB activity depends on direct cell contact.
pubmed:grant
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/19775197-10028917, http://linkedlifedata.com/resource/pubmed/commentcorrection/19775197-10485684, http://linkedlifedata.com/resource/pubmed/commentcorrection/19775197-10671706, http://linkedlifedata.com/resource/pubmed/commentcorrection/19775197-11340257, http://linkedlifedata.com/resource/pubmed/commentcorrection/19775197-11425931, http://linkedlifedata.com/resource/pubmed/commentcorrection/19775197-11869029, http://linkedlifedata.com/resource/pubmed/commentcorrection/19775197-12193778, http://linkedlifedata.com/resource/pubmed/commentcorrection/19775197-12781987, http://linkedlifedata.com/resource/pubmed/commentcorrection/19775197-15494428, http://linkedlifedata.com/resource/pubmed/commentcorrection/19775197-15509325, http://linkedlifedata.com/resource/pubmed/commentcorrection/19775197-16322639, http://linkedlifedata.com/resource/pubmed/commentcorrection/19775197-16730352, http://linkedlifedata.com/resource/pubmed/commentcorrection/19775197-16873764, http://linkedlifedata.com/resource/pubmed/commentcorrection/19775197-17679775, http://linkedlifedata.com/resource/pubmed/commentcorrection/19775197-17936031, http://linkedlifedata.com/resource/pubmed/commentcorrection/19775197-18212649, http://linkedlifedata.com/resource/pubmed/commentcorrection/19775197-18323495, http://linkedlifedata.com/resource/pubmed/commentcorrection/19775197-18384759, http://linkedlifedata.com/resource/pubmed/commentcorrection/19775197-18418770, http://linkedlifedata.com/resource/pubmed/commentcorrection/19775197-18420947, http://linkedlifedata.com/resource/pubmed/commentcorrection/19775197-18580536, http://linkedlifedata.com/resource/pubmed/commentcorrection/19775197-18694578, http://linkedlifedata.com/resource/pubmed/commentcorrection/19775197-19081024, http://linkedlifedata.com/resource/pubmed/commentcorrection/19775197-19098906, http://linkedlifedata.com/resource/pubmed/commentcorrection/19775197-19132123, http://linkedlifedata.com/resource/pubmed/commentcorrection/19775197-19202439, http://linkedlifedata.com/resource/pubmed/commentcorrection/19775197-3193461
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1557-8534
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
19
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
867-76
pubmed:dateRevised
2010-9-28
pubmed:meshHeading
pubmed-meshheading:19775197-Animals, pubmed-meshheading:19775197-Brain, pubmed-meshheading:19775197-Cell Proliferation, pubmed-meshheading:19775197-Coculture Techniques, pubmed-meshheading:19775197-Culture Media, pubmed-meshheading:19775197-Cytoprotection, pubmed-meshheading:19775197-Gene Expression Regulation, pubmed-meshheading:19775197-Injections, Spinal, pubmed-meshheading:19775197-Interleukin-6, pubmed-meshheading:19775197-Luciferases, pubmed-meshheading:19775197-Male, pubmed-meshheading:19775197-Mesenchymal Stem Cell Transplantation, pubmed-meshheading:19775197-Mesenchymal Stem Cells, pubmed-meshheading:19775197-Models, Biological, pubmed-meshheading:19775197-NF-kappa B, pubmed-meshheading:19775197-Neurons, pubmed-meshheading:19775197-Prosthesis Implantation, pubmed-meshheading:19775197-Rats, pubmed-meshheading:19775197-Rats, Sprague-Dawley, pubmed-meshheading:19775197-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:19775197-Stromal Cells, pubmed-meshheading:19775197-Tumor Necrosis Factor-alpha
pubmed:year
2010
pubmed:articleTitle
Direct intrathecal implantation of mesenchymal stromal cells leads to enhanced neuroprotection via an NFkappaB-mediated increase in interleukin-6 production.
pubmed:affiliation
Department of Surgery, University of Texas Medical School at Houston, Houston, Texas 77030, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural