Effect of stromal-cell-derived factor 1 on stem-cell homing and tissue regeneration in ischaemic cardiomyopathy
Effect of stromal-cell-derived factor 1 on stem-cell homing and tissue regeneration in ischaemic cardiomyopathy
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DOI：
10.1016/s0140-6736(03)14232-8
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发表时间：
2003-08-30
期刊：
影响因子：
168.9
通讯作者：
Penn, MS
中科院分区：
文献类型：
--
作者：
Askari, AT;Unzek, S;Penn, MS
背景：心肌梗死时通过干细胞动员实现心肌再生是已知的，尽管干细胞随后归家到梗死组织的机制以及这种方法是否可用于缺血性心肌病的治疗尚不清楚。我们在缺血性心肌病的Lewis大鼠模型（左前降支结扎）中研究了这些问题。方法研究了粒细胞集落刺激因子（非格司提姆）在同基因细胞移植和非同基因细胞移植时对干细胞动员的影响。超声心动图量化组织多普勒成像的缩短分数和心肌应变。研究结果：单用非格昔汀进行干细胞动员不能导致骨髓源性细胞的移植。骨髓干细胞归巢所需的基质细胞衍生因子1 （SDF-1）在心肌梗死后立即上调，并在7天内下调。心肌梗死后8周，将稳定转染表达SDF-1的同基因心肌成纤维细胞移植到梗死周围区，非格昔汀给药后诱导cd117阳性干细胞归巢至损伤心肌（对照与表达SDF-1的心肌成纤维细胞平均7.2 [sdf - 3.4] vs 33.2[6.0]个细胞/mm）(2)，每组n=4, p
Background Myocardial regeneration via stem-cell mobilisation at the time of myocardial infarction is known to occur, although the mechanism for stem-cell homing to infarcted tissue subsequently and whether this approach can be used for treatment of ischaemic cardiomyopathy are unknown. We investigated these issues in a Lewis rat model (ligation of the left anterior descending artery) of ischaemic cardiomyopathy.Methods We studied the effects of stem-cell mobilisation by use of granulocyte colony-stimulating factor (filgrastim) with or without transplantation of syngeneic cells. Shortening fraction and myocardial strain by tissue doppler imaging were quantified by echocardiography.Findings Stem-cell mobilisation with filgrastim alone did not lead to engraftment of bone-marrow-derived cells. Stromal-cell-derived factor 1 (SDF-1), required for stem-cell homing to bone marrow, was upregulated immediately after myocardial infarction and downregulated within 7 days. 8 weeks after myocardial infarction, transplantation into the peri-infarct zone of syngeneic cardiac fibroblasts stably transfected to express SDF-1 induced homing of CD117-positive stem cells to injured myocardium after filgrastim administration (control vs SDF-1-expressing cardiac fibroblasts mean 7.2 [SD 3.4] vs 33.2 [6.0] cells/mm(2), n=4 per group, p