Department of Neurology, Second Affiliated Hospital, Harbin Medical University, Harbin 150086, China.
BMC Neurosci. 2011 Jun 24;12:61. doi: 10.1186/1471-2202-12-61.
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.
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.
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.
骨髓单个核细胞(BMMC)移植是治疗脑缺血的一种很有前途的方法;然而,对于其治疗效果是否可以通过体内共给予潜在调节因子来改善,目前知之甚少。为了探索这种可能性,本研究检查了 BMMC 和 G-CSF 对实验性脑缺血中细胞增殖、早期神经元发育和神经功能恢复的影响,与既未接受治疗也未接受治疗的对照组相比。
BMMC+G-CSF 组的缺血/梗死面积明显小于仅接受 BMMC 治疗、仅接受 G-CSF 治疗或生理盐水治疗的动物组。发现移植的 BMMC 与增殖细胞核抗原(PCNA)和未成熟神经元标志物双皮质素(DCX)共定位。BMMC+G-CSF 组在时间依赖性方式下,PCNA 和 DCX 表达细胞的数量密度增加,在粘贴标签去除试验中的表现提高,神经功能严重程度评分降低,均优于其他组。
BMMC 和 G-CSF 联合应用具有协同的有益作用。这种作用至少部分可能与骨髓干细胞增殖和分化的增加以及宿主大脑的再生和功能恢复增强有关。结果表明,G-CSF 可以提高实验性脑缺血小鼠模型中 BMMC 移植的治疗效果。