Bone marrow mononuclear cells have neurovascular tropism and improve diabetic neuropathy.

Bone marrow mononuclear cells have neurovascular tropism and improve diabetic neuropathy.
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DOI:
10.1002/stem.87
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发表时间:
2009-07
期刊:
影响因子:
5.2
通讯作者:
Yoon, Young-sup
Yoon, Young-sup
中科院分区:
医学2区
文献类型:
--
作者:
Kim, Hyongbum;Park, Jong-seon;Choi, Yong Jin;Kim, Mee-Ohk;Huh, Yang Hoon;Kim, Sung-Whan;Han, Ji Woong;Lee, JiYoon;Kim, Sinae;Houge, Mackenzie A.;Ii, Masaaki;Yoon, Young-sup

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骨髓来源的单核细胞(BMNCs)已被证明可以有效治疗缺血性心血管疾病。由于糖尿病神经病变(DN)与血管生成受损和神经中血管生成因子和神经营养因子缺乏有因果关系,因此我们研究了局部注射BMNCs是否可以改善DN。严重的周围神经病变,其特征在于运动和感觉神经传导速度(NCV)的显着下降,开发后12周的糖尿病与链脲佐菌素诱导大鼠。BMNCs的注射使运动和感觉NCV恢复到正常水平,并在4周内显著改善糖尿病神经中的血管密度和血流量。荧光显微镜观察显示DiI标记的BMNCs优先植入坐骨神经。整体安装的荧光成像和共聚焦显微镜评价表明,许多BMNCs本地化的神经血管的过程中密切接近血管,而不纳入神经血管作为内皮细胞在可检测的水平。实时荧光定量逆转录聚合酶链反应分析表明,血管生成和神经营养因子的水平显着增加的神经BMNC注射。局部移植骨髓单个核细胞通过促进周围神经血管生成和增加血管生成因子和神经营养因子来改善实验性DN。这些结果表明,骨髓单个核细胞移植可能是治疗DN的一种新的治疗选择。
Bone marrow-derived mononuclear cells (BMNCs) have been shown to effectively treat ischemic cardiovascular diseases. Because diabetic neuropathy (DN) is causally associated with impaired angiogenesis and deficiency of angiogenic and neurotrophic factors in the nerves, we investigated whether DN can be ameliorated by local injection of BMNCs. Severe peripheral neuropathy, characterized by a significant decrease in the motor and sensory nerve conduction velocities (NCVs), developed 12 weeks after the induction of diabetes with streptozotocin in rats. The injection of BMNCs restored motor and sensory NCVs to normal levels and significantly improved vascular density and blood flow in diabetic nerves over 4 weeks. Fluorescent microscopic observation revealed that DiI-labeled BMNCs preferentially engrafted in sciatic nerves. Whole-mount fluorescent imaging and confocal microscopic evaluation demonstrated that many of the BMNCs localized following the course of the vasa nervorum in close proximity to blood vessels without incorporation into vasa nervorum as endothelial cells at a detectable level. Real-time reverse transcription-polymerase chain reaction analysis showed that the levels of angiogenic and neurotrophic factors were significantly increased in the nerves by BMNC injection. Local transplantation of BMNCs improved experimental DN by augmenting angiogenesis and increasing angiogenic and neurotrophic factors in peripheral nerves. These findings suggest that BMNC transplantation may represent a novel therapeutic option for treating DN.
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