کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
9894494 | 1542461 | 2005 | 8 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Mobilizing of haematopoietic stem cells to ischemic myocardium by plasmid-mediated stromal-cell-derived factor-1α treatment
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موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
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چکیده انگلیسی
A concentration gradient of stromal-cell-derived factor-1α (SDF-1α) is the major mechanism for homing of haematopoietic stem cells (HSCs) in bone marrow. We tested the hypothesis that a gene therapy using SDF-1α can enhance HSCs recruiting to the heart upon myocardial infarction (MI). Adult mice with surgically induced myocardial ischemia were injected intramyocardially with either saline (n=12) or SDF-1α plasmid (n=12) in 50 μl volume in the ischemic border zone of the infarcted heart 2 weeks after myocardial infarction. Donor Lin-c-kit+ HSCs from isogenic BalB/c mice were harvested, sorted through magnetic cell sorting (MACS) and labeled with PKH26 Red. Three days after plasmid or saline injection, 1Ã105 labeled cells were injected intravenously (i.v.) into saline mice (n=4) and SDF-1α plasmid mice (n=4). The hearts and other tissue were removed for Western blot assay 2 weeks after plasmid or saline treatment. The labeled Lin-c-kit+ cells were identified with immunofluoresent staining and endogenous c-kit+ cells were identified by immunohistochemical staining. In mice killed at 1 month postinfarct, Western blot showed higher levels of SDF-1α expression in SDF-1α-treated mouse ischemic hearts compared to saline-treated hearts and other tissues. In the SDF-1α plasmid-treated hearts, SDF-1α is overexpressed in the periinfarct zone. The labeled stem cells engrafted to the SDF-1α positive site in the myocardium. There was also evidence for endogenous stem cell recruiting. The density of c-kit+ cells in border zone, an index of endogenous stem cell mobilization, was significantly higher in the SDF-1α-treated group than in the saline group (14.63±1.068 cells/hpf vs. 11.31±0.65 cells/hpf, P=0.013) at 2 weeks after SDF-1α or saline treatment. Following myocardial infarction, treatment with SDF-1α recruits stem cells to damaged heart where they may have a role in repairing and regeneration. The gene therapy with an SDF-1α vector offers a promising therapeutic strategy for mobilizing stem cells to the ischemic myocardium.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Regulatory Peptides - Volume 125, Issues 1â3, 15 February 2005, Pages 1-8
Journal: Regulatory Peptides - Volume 125, Issues 1â3, 15 February 2005, Pages 1-8
نویسندگان
Yao Liang Tang, Keping Qian, Y. Clare Zhang, Leping Shen, M. Ian Phillips,