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用于心脏细胞治疗的治疗相关人血管生成祖细胞的体外功能比较。

In vitro functional comparison of therapeutically relevant human vasculogenic progenitor cells used for cardiac cell therapy.

机构信息

Division of Cardiac Surgery, University of Ottawa Heart Institute, Ottawa, Ontario, Canada.

出版信息

J Thorac Cardiovasc Surg. 2010 Jul;140(1):216-24, 224.e1-4. doi: 10.1016/j.jtcvs.2009.11.016. Epub 2010 Feb 18.

DOI:10.1016/j.jtcvs.2009.11.016
PMID:20167338
Abstract

OBJECTIVE

In cardiac cell therapy almost every cell type tested experimentally has yielded some benefit. However, there is a lack of studies directly comparing the function of various stem/progenitor cell populations. This study describes the expansion of peripheral blood CD133(+) cells and compares their functional properties with those of other commonly used human progenitor cell populations.

METHODS

CD133(+) cells were generated from the CD133(-) fraction of peripheral blood, either serially (pooled-derived) or after 14 days of culture (derived). Their phenotypic, migratory, and vasculogenic properties were compared with those of 4 commonly used progenitor cell populations in vitro.

RESULTS

Serial expansion resulted in an 11-fold increase in the number of CD133(+) cells. The proportion of derived CD133(+) cells collected between 0 and 8 days also expressing CD34 and vascular endothelial growth factor receptor 2 was similar (approximately 60%, P = .41). Adherent, 4-day cultured endothelial progenitor cells demonstrated enhanced migration compared with each of the other 5 cell populations (all P < or = .002). The migration of derived CD133(+) progenitors was enhanced by coculture with CD133(-) cells or their supernatant (P < .05). In vitro vasculogenesis assays revealed that derived and pooled-derived CD133(+) cells had superior vasculogenic potential compared with other progenitor populations (P < or = .03).

CONCLUSIONS

A novel source of expandable CD133(+) cells can be generated from the CD133(-) fraction of peripheral blood. The CD133 phenotypic marker translates into the cell being vasculogenically more potent in vitro, which could be beneficial to inducing vasculogenesis in the ischemic heart. Furthermore, intercellular interactions appear important for improving the therapeutic efficacy of cell transplantation.

摘要

目的

在心脏细胞治疗中,几乎每种经实验测试的细胞类型都产生了一定的益处。然而,缺乏直接比较各种干细胞/祖细胞群体功能的研究。本研究描述了外周血 CD133(+)细胞的扩增,并比较了其与其他常用的人类祖细胞群体的功能特性。

方法

从外周血的 CD133(-)部分生成 CD133(+)细胞,无论是连续(汇集衍生)还是培养 14 天后(衍生)。将其表型、迁移和血管生成特性与体外 4 种常用祖细胞群体进行比较。

结果

连续扩增使 CD133(+)细胞的数量增加了 11 倍。在 0 至 8 天期间收集的衍生 CD133(+)细胞中也表达 CD34 和血管内皮生长因子受体 2 的比例相似(约 60%,P =.41)。与其他 5 种细胞群体相比,贴壁培养 4 天的内皮祖细胞表现出增强的迁移能力(所有 P < 或 =.002)。衍生 CD133(+)祖细胞的迁移能力通过与 CD133(-)细胞或其上清液共培养而增强(P <.05)。体外血管生成测定显示,衍生和汇集衍生的 CD133(+)细胞与其他祖细胞群体相比具有更好的血管生成潜力(P < 或 =.03)。

结论

可以从外周血的 CD133(-)部分生成可扩增的 CD133(+)细胞的新来源。CD133 表型标志物转化为细胞在体外具有更强的血管生成能力,这可能有益于诱导缺血性心脏中的血管生成。此外,细胞间相互作用对于改善细胞移植的治疗效果似乎很重要。

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