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Open Access Highly Accessed Research article

Granulocyte colony-stimulating factor increases the therapeutic efficacy of bone marrow mononuclear cell transplantation in cerebral ischemia in mice

Xue-Mei Zhang1, Fang Du1, Dan Yang1, Rui Wang1, Chun-Jiang Yu1, Xiang-Nan Huang1, Hong-Yan Hu2, Wei Liu3 and Jin Fu1*

Author affiliations

1 Department of Neurology, Second Affiliated Hospital, Harbin Medical University, Harbin, 150086, China

2 Department of Science Research Management, Second Affiliated Hospital, Harbin Medical University, Harbin, 150086, China

3 Center for Experimental Research, Second Affiliated Hospital, Harbin Medical University, Harbin, 150086, China

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Citation and License

BMC Neuroscience 2011, 12:61  doi:10.1186/1471-2202-12-61

Published: 24 June 2011

Abstract

Background

Bone 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.

Result

Ischemia/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.

Conclusion

BMMCs 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.