权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Effect of cytokines in the acute ischemic tissue on the survival and differentiation of bone marrow cells

急性缺血组织细胞因子对骨髓细胞存活和分化的影响

基本信息

批准号：
18591413
负责人：
FURUTANI Akira
金额：
$ 2.53万
依托单位：
Yamaguchi University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18591413/
关键词：
Ischemia Bone marrow stem cells Cytokines

项目摘要

Therapeutic angiogenesis by bone marrow cells (BMCs) implantation is a promising treatment for ischemic diseases. It is well known that many inflammatory cytokines are released in ischemic tissue, especially in the acute phase. We investigated whether the transient increase of cytokines in the acute ischemic tissue influences cell-based therapeutic angiogenesis.Ischemic limb models were created in C57BL/6 mice and used 24 hours (acute) or 2 weeks (chronic) after ischemia. We extracted total tissue protein from the acute and chronic ischemic limbs muscles and found that inflammatory cytokines (IL-1β, bFGF, and MCP-1) were robustly increased in acute ischemic limbs, but that this increase had almost disappeared in the chronic ischemic limbs. The survival, adhesion, and migration of BMCs were significantly better after culture with 1 mg/ml tissue protein from the acute ischemic limbs than with that from the chronic ischemic and non-ischemic limbs (p < 0.05) ; however, the difference was relatively weak between the chronic ischemic limbs and the non-ischemic limbs. For the in vivo study, we implanted BMCs into the acute and chronic ischemic limbs of mice. The survival of BMCs was significantly better in the acute ischemic limbs than in the chronic ischemic limbs (p < 0.01). Compared with control treatment, improved blood flow was seen in the acute ischemic limbs (p < 0.01), but not in the chronic ischemic limbs (p = 0.27). The endothelial differentiation of surviving BMCs was found in the acute ischemic limbs.Our findings suggest that the transient increase of cytokines in the acute ischemic tissue is beneficial for cell-based therapeutic angiogenesis.

骨髓细胞移植治疗性血管新生是一种很有前途的治疗缺血性疾病的方法。众所周知，许多炎性细胞因子在缺血组织中释放，特别是在急性期。我们研究了急性缺血组织中细胞因子的瞬时增加是否影响基于细胞的治疗性血管生成。在C57 BL/6小鼠中建立缺血肢体模型，并在缺血后24小时（急性）或2周（慢性）使用。我们从急性和慢性缺血肢体肌肉中提取总组织蛋白，发现急性缺血肢体中炎性细胞因子（IL-1β、bFGF和MCP-1）显著增加，但在慢性缺血肢体中这种增加几乎消失。1 mg/ml组织蛋白培养急性缺血肢体的BMCs的存活、粘附和迁移能力明显好于慢性缺血和非缺血肢体（p < 0.05），但慢性缺血肢体与非缺血肢体之间的差异相对较弱。对于体内研究，我们将BMCs植入小鼠的急性和慢性缺血肢体。急性缺血肢体的BMCs存活率明显高于慢性缺血肢体（P < 0.01）。与对照治疗相比，在急性缺血肢体中观察到血流改善（p < 0.01），但在慢性缺血肢体中没有观察到血流改善（p = 0.27）。在急性缺血肢体中发现存活的BMCs向内皮细胞分化，我们的研究结果表明急性缺血组织中细胞因子的短暂增加有利于以细胞为基础的治疗性血管生成。