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CD34 细胞端粒长度和 hTERT 表达对慢性心力衰竭患者自体 CD34 细胞移植结局的影响。

The effect of CD34 cell telomere length and hTERT expression on the outcome of autologous CD34 cell transplantation in patients with chronic heart failure.

机构信息

Blood Transfusion Centre of Slovenia, Ljubljana, Slovenia.

Institute for Biostatistics and Medical Informatics, Faculty of Medicine Ljubljana, Ljubljana, Slovenia.

出版信息

Mech Ageing Dev. 2017 Sep;166:42-47. doi: 10.1016/j.mad.2017.06.001. Epub 2017 Jun 19.

Abstract

Age-related telomere attrition in stem/progenitor cells may diminish their functional capacity and thereby impair the outcome of cell-based therapies. The aim of the present study was to investigate the effect of CD34 cell telomere length and hTERT expression on the clinical outcome of autologous CD34 cell transplantation. We studied 43 patients with cardiomyopathy. Their peripheral blood CD34 cells were mobilized with granulocyte colony-stimulating factor, enriched by immunoselection and delivered transendocardially. Relative telomere length and expression levels of hTERT were measured using a real-time PCR assay. Immunoselected CD34 cells had longer telomere length compared to leukocytes in leukapheresis products (p=0.001). In multivariate analysis, CD34 cell telomere length was not associated with the clinical outcome (b=3.306, p=0.540). While hTERT expression was undetectable in all leukapheresis products, 94.4% of the CD34 enriched cell products expressed hTERT. Higher CD34hTERT expression was associated with a better clinical outcome on univariate analysis (b=87.911, p=0.047). Our findings demonstrate that CD34 cell telomere length may not influence the clinical outcome in cardiomyopathy patients treated with autologous CD34 cell transplantation. Larger studies are needed to validate the impact of the CD34hTERT expression on the clinical outcome of autologous CD34 cell transplantation.

摘要

与年龄相关的端粒损耗可能会降低干细胞/祖细胞的功能能力,从而损害基于细胞的治疗的效果。本研究旨在探讨 CD34 细胞端粒长度和 hTERT 表达对自体 CD34 细胞移植临床结果的影响。我们研究了 43 例心肌病患者。他们的外周血 CD34 细胞用粒细胞集落刺激因子动员,通过免疫选择富集,并经心内膜给药。使用实时 PCR 测定法测量相对端粒长度和 hTERT 的表达水平。与白细胞相比,免疫选择的 CD34 细胞在白细胞分离产物中的端粒长度更长(p=0.001)。在多变量分析中,CD34 细胞端粒长度与临床结果无关(b=3.306,p=0.540)。虽然所有白细胞分离产物中均未检测到 hTERT 表达,但 94.4%的 CD34 富集细胞产物表达 hTERT。在单变量分析中,较高的 CD34hTERT 表达与更好的临床结果相关(b=87.911,p=0.047)。我们的研究结果表明,在接受自体 CD34 细胞移植治疗的心肌病患者中,CD34 细胞端粒长度可能不会影响临床结果。需要更大的研究来验证 CD34hTERT 表达对自体 CD34 细胞移植临床结果的影响。

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