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在体外扩增过程中,与间充质基质细胞直接接触会影响CD133+造血干细胞的迁移行为和基因表达谱。

Direct contact with mesenchymal stromal cells affects migratory behavior and gene expression profile of CD133+ hematopoietic stem cells during ex vivo expansion.

作者信息

Alakel Nael, Jing Duohui, Muller Katrin, Bornhauser Martin, Ehninger Gerhard, Ordemann Rainer

机构信息

Medizinische Klinik und Poliklinik I, University Hospital Carl-Gustav-Carus, Dresden, Germany.

出版信息

Exp Hematol. 2009 Apr;37(4):504-13. doi: 10.1016/j.exphem.2008.12.005. Epub 2009 Feb 12.

DOI:10.1016/j.exphem.2008.12.005
PMID:19216019
Abstract

OBJECTIVE

To investigate the impact of direct contact between mesenchymal stromal cells (MSCs) and CD133(+) hematopoietic stem cells in terms of expansion potential, differentiation, migratory capacity, and gene expression profile.

MATERIALS AND METHODS

CD133(+)-purified hematopoietic progenitor cells were cultured for 7 days on subconfluent MSCs supplemented with growth-factor-containing medium. After ex vivo expansion, nonadherent and adherent cells were collected and analyzed separately.

RESULTS

The adherent cell population was less differentiated than the nonadherent fraction. CXCR4 was upregulated in the adherent fraction, which was associated with a higher migration capacity toward a stromal cell-derived factor-1 gradient. Colony-forming unit granulocyte-macrophage and long-term culture-initiation cell assays demonstrated a higher clonogenicity and repopulating capacity of the adherent fraction. Genes involved in adhesion, cell-cycle control, motility, and self-renewal were more highly expressed in the adherent fraction.

CONCLUSION

Adhesion and direct cell-to-cell contact with an MSC feeder layer supports ex vivo expansion, migratory potential, and stemness of CD133(+) hematopoietic progenitor cells.

摘要

目的

研究间充质基质细胞(MSC)与CD133(+)造血干细胞直接接触对其扩增潜能、分化、迁移能力及基因表达谱的影响。

材料与方法

将纯化的CD133(+)造血祖细胞在补充含生长因子培养基的亚汇合MSC上培养7天。体外扩增后,分别收集非贴壁细胞和贴壁细胞并进行分析。

结果

贴壁细胞群体的分化程度低于非贴壁部分。CXCR4在贴壁部分上调,这与对基质细胞衍生因子-1梯度更高的迁移能力相关。集落形成单位粒细胞-巨噬细胞和长期培养起始细胞试验表明贴壁部分具有更高的克隆形成能力和再增殖能力。参与黏附、细胞周期调控、运动性和自我更新的基因在贴壁部分表达更高。

结论

与MSC饲养层的黏附及细胞间直接接触支持CD133(+)造血祖细胞的体外扩增、迁移潜能及干性。

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