Abstract
BackgroundBone marrow mononuclear cell (BMMC) transplantation is a promising therapy for cerebral ischemia; however, little is known if its therapeutic efficacy may be improved by co-administration of potential modulatory factors in vivo. To explore this possibility, the present study examined the effect of BMMCs and G-CSF on cell proliferation, early neuronal development and neurological function recovery in experimental cerebral ischemia relative to controls that received neither treatment.ResultIschemia/infarct area was significantly reduced in BMMCs+G-CSF group relative to animal groups treated with BMMCs only, G-CSF only or saline. Transplanted BMMCs were found to colocalize with the proliferative cell nuclear antigen (PCNA) and the immature neuronal marker doublecortin (DCX). The BMMCs+G-CSF group showed increased numerical density of cells expressing PCNA and DCX, improved performance in adhesive sticker removal test and reduced neurological function severity scores relative to other groups in a time-dependent manner.ConclusionBMMCs and G-CSF co-administration exhibits synergistic beneficial effect over time. This effect could be at least partially related to increased proliferation and differentiation of bone marrow stem cells and enhanced host brain regeneration and functional recovery. The results suggest that G-CSF can increase the therapeutic efficacy of BMMCs transplantation in an experimental mouse model of cerebral ischemia.
Highlights
Bone marrow mononuclear cell (BMMC) transplantation is a promising therapy for cerebral ischemia; little is known if its therapeutic efficacy may be improved by co-administration of potential modulatory factors in vivo
We characterized BMMCs harvested from the donor mice to obtain their surface antigen profile by fluorescence-activated cell sorting (FACS)
Effect of Granulocyte colony stimulating factor (G-CSF) and BMMCs on cerebral infarct size In the present study, effect of BMMC transplantation and G-CSF co-administration following experimental cerebral ischemia was comparatively studied among 4 groups of mice
Summary
Bone marrow mononuclear cell (BMMC) transplantation is a promising therapy for cerebral ischemia; little is known if its therapeutic efficacy may be improved by co-administration of potential modulatory factors in vivo. To explore this possibility, the present study examined the effect of BMMCs and G-CSF on cell proliferation, early neuronal development and neurological function recovery in experimental cerebral ischemia relative to controls that received neither treatment. Granulocyte colony stimulating factor (G-CSF) is one of such biological modulators, and has been shown to enhance proliferation and mobilization of BMMCs in
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