Circulating stem cell vary with NYHA stage in heart failure patients.

Circulating stem cell vary with NYHA stage in heart failure patients.
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心力衰竭患者的循环干细胞随 NYHA 分期的不同而变化。

DOI:
10.1111/j.1582-4934.2010.01195.x
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发表时间:
2011-08
影响因子:
5.3
通讯作者:
Beltrami CA
Beltrami CA
中科院分区:
医学2区
文献类型:
--
作者:
Fortini C;Toffoletto B;Fucili A;Puppato E;Olivares A;Beltrami AP;Fiorelli V;Bergamin N;Cesselli D;Morelli C;Francolini G;Ferrari R;Beltrami CA

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我们检测了心力衰竭(HF)患者不同病理阶段外周血中干细胞亚类[间充质干细胞(MSCs)、造血干细胞(HSCs)、内皮祖细胞/循环内皮细胞(EPC/CECs)和组织承诺干细胞(TCSCs)]的水平,并与血浆促血管生成细胞因子水平进行了相关性研究。对97例心衰患者(NYHA I级24例,II级41例,III级17例,IV级15例)和23例健康对照的外周血中干细胞水平进行了分析。测定血浆中血小板衍生生长因子-BB、碱性成纤维细胞生长因子、肝细胞生长因子、血管内皮生长因子、血管内皮生长因子-1α、肿瘤坏死因子-α和肿瘤坏死因子-脑钠素的水平。与健康人相比,心功能IV级患者骨髓间充质干细胞,尤其是CD45−CD34−CD90+、CD45−CD34−CD105+和CD45−CD34−CXCR4+显著升高(分别是正常人的16.8倍、6.4倍和2.7倍)。CD45CD34−−CD90+CXCR4+细胞水平从II级到IV级逐渐升高(分别是对照组的8.5%、12%和21.5%)。CD45+CD34+CXCR4+亚群(CD45+CD34+CD90+CXCR4+,在对照组中CD45+CD34+CD90+CXCR4+,分别为1.4Cells/μL和13.3Cells/μL)和TCSC(对照组CD45CD34+CXCR4+,1.5Cells/μL,在NYHAII级和IV级患者中分别为12.4Cells/μL和28.6Cells/cxCR4+)。所有检测的细胞因子在心力衰竭患者中均增强。特别是,对于PDGF-BB和SDF-1α,我们研究了特定的配体/受体对。有趣的是,前者与表达PDGFR的TCSCs呈正相关(r=0.52P=0.001),后者与表达CXCR4的TCSCs呈正相关(r=0.34,P=0.005),与表达CXCR4的MSCs CD90+呈正相关(r=0.39P=0.001)。心力衰竭的特征是不同的MSC、HSC、EPC和TCSC亚群循环水平的增加。这一过程的实体和动力学在不同的细胞亚群中各不相同。具体地说,与HSC和EPC/CECs不同,MSCs和TCSCs随着疾病的进展而显著增加,提示这些细胞在HF的病理生理学中可能起着不同的作用。
We have investigated the blood levels of sub-classes of stem cells (SCs) [mesenchymal stem cells (MSCs), haematopoietic stem cells (HSCs), endothelial progenitor cells/circulating endothelial cells (EPCs/CECs) and tissue-committed stem cells (TCSCs)] in heart failure (HF) patients at different stage of pathology and correlated it with plasmatic levels of proangiogenic cytokines. Peripheral blood level of SCs were analysed in 97 HF patients (24 in NYHA class I, 41 in class II, 17 in class III and 15 in class IV) and in 23 healthy controls. Plasmatic levels of PDGF-BB, bFGF, HGF, vascular endothelial growth factor (VEGF), SDF-1α, TNF-α and NTproBNP were also measured. Compared with healthy individuals, MSC, and in particular the sub-classes CD45−CD34−CD90+, CD45−CD34−CD105+ and CD45−CD34−CXCR4+ were significantly enhanced in NYHA class IV patients (16.8-, 6.4- and 2.7-fold, respectively). Level of CD45−CD34−CD90+CXCR4+cells progressively increased from class II to class IV (fold increases compared with controls: 8.5, 12 and 21.5, respectively). A significant involvement of CXCR4+ subpopulation of HSC (CD45+CD34+CD90+CXCR4+, 1.4 versus 13.3 cells/μl in controls and NYHA class III patients, respectively) and TCSC (CD45−CD34+CXCR4+, 1.5 cells/ μl in controls versus 12.4 and 28.6 cells/μl in NYHA classes II and IV, respectively) were also observed. All tested cytokines were enhanced in HF patients. In particular, for PDGF-BB and SDF-1α we studied specific ligand/receptors pairs. Interestingly, the first one positively correlated with TCSCs expressing PDGFR (r = 0.52, P = 0.001), whereas the second one correlated with TCSCs (r = 0.34, P = 0.005) and with MSCs CD90+ expressing CXCR4 (r = 0.39, P = 0.001). HF is characterized by the increase in the circulating levels of different MSC, HSC, EPC and TCSC subsets. Both the entity and kinetic of this process varied in distinct cell subsets. Specifically, differently from HSCs and EPCs/CECs, MSCs and TCSCs significantly increased with the progression of the disease, suggesting a possible distinct role of these cells in the pathophysiology of HF.
DOI: 10.1158/0008-5472.can-04-1874
发表时间: 2005-04-15
期刊: CANCER RESEARCH
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