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Human umbilical cord blood cell therapy blocks the morphological change and recruitment of CD11b‐expressing, isolectin‐binding proinflammatory cells after middle cerebral artery occlusion
Author(s) -
Leonardo Christopher C.,
Hall Aaron A.,
Collier Lisa A.,
Ajmo Craig T.,
Willing Alison E.,
Pennypacker Keith R.
Publication year - 2009
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.22306
Subject(s) - proinflammatory cytokine , microglia , neuroinflammation , integrin alpha m , immune system , cell , medicine , immunology , microbiology and biotechnology , biology , inflammation , biochemistry
Secondary neurodegeneration resulting from stroke is mediated by delayed proinflammatory signaling and immune cell activation. Although it remains unknown which cell surface markers signify a proinflammatory phenotype, increased isolectin binding occurs on CD11b‐expressing immune cells within injured brain tissue. Several reports have confirmed the efficacy of human umbilical cord blood (HUCB) cell therapy in reducing ischemic injury in rat after middle cerebral artery occlusion (MCAO), and these effects were attributed in part to dampened neuroinflammation. The present study examined the time course of lectin binding to cells of microglia/macrophage lineage within 96 hr after MCAO and whether delayed HUCB cell treatment alters the migration and/or morphological characteristics of these cells throughout the period of infarct expansion. Isolectin binding was up‐regulated in response to injury, was maximal at 96 hr, and colocalized with cells that expressed the putative proinflammatory markers MMP‐9 and nitric oxide. Isolectin‐tagged fluorescence was also significantly increased at 72 hr and localized to greater numbers of amoeboid, CD11b‐expressing cells relative to 51 hr. Treatment with 1 × 10 6 HUCB cells significantly reduced total lectin binding at 72 hr, as well as the total area occupied by lectin‐tagged fluorescence at both 51 and 72 hr, relative to vehicle‐treated controls. This effect was accompanied by a shift in the morphology of CD11b‐positive cells from amoeboid to ramified shape. These data indicate that HUCB cell therapy suppressed the recruitment of proinflammatory, isolectin‐binding cells during the period of infarct expansion, thus offering a potential mechanism for the protective effects of HUCB cell therapy. © 2009 Wiley‐Liss, Inc.