Functional nanofiber scaffolds with different spacers modulate adhesion and expansion of cryopreserved umbilical cord blood hematopoietic stem/progenitor cells
Functional nanofiber scaffolds with different spacers modulate adhesion and expansion of cryopreserved umbilical cord blood hematopoietic stem/progenitor cells
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DOI：
10.1016/j.exphem.2007.02.002
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发表时间：
2007-05-01
影响因子：
2.6
通讯作者：
Mao, Hai-Quan
中科院分区：
文献类型：
--
作者：
Chua, Kian-Ngiap;Chai, Chou;Mao, Hai-Quan
Objective.制备了通过不同间隔基（分别为乙烯、丁烯和己烯）与纤维表面缀合的氨基的纳米纤维支架，并研究了间隔基长度对脐带血造血干/祖细胞（HSPCs）粘附和扩增的影响。电纺聚合物纤维素支架功能化与聚（丙烯酸）接枝，然后通过共轭的氨基与不同的间隔。HSPC在胺化支架上扩增10天。在扩增培养后评价扩增细胞的细胞增殖、表面标志物表达、克隆形成潜力和非肥胖糖尿病（NOD）/严重联合免疫缺陷（SCID）再增殖潜力。具有乙烯和丁烯间隔基的胺化的支架显示出高扩增效率（总细胞扩增773倍和805倍，CD 34（+）CD 45（+）细胞扩增200倍和235倍）。HSPC在具有己烯间隔基的胺化支架上的增殖显著较低（总细胞扩增210倍，CD 34（+）CD 45（+）细胞扩增86倍），但保持最高的CD 34（+）CD 45（+）细胞分数（41.1%）。3种氨基化纳米纤维支架上扩增的HSPCs集落形成单位粒细胞-红细胞-单核细胞-巨核细胞和长期培养起始细胞维持率相似;然而，氨基乙基和氨基丁基纳米纤维上扩增的HSPCs在NOD/SCID小鼠体内的移植潜力显著高于氨基己基纳米纤维。该研究表明，胺化纳米纤维是用于离体HSPC扩增的上级基底，这与HSPC与这些胺化纳米纤维的粘附增强相关。氨基通过间隔基与载体表面结合，影响扩增结果。我们的研究结果强调了支架拓扑结构和细胞-基质相互作用对调节HSPC增殖和补充精氨酸的扩增中的自我更新的重要性。(c)2007年国际实验血液学学会。爱思唯尔公司出版
Objective. Nanofiber scaffolds with amino groups conjugated to fiber surface through different spacers (ethylene, butylenes, and hexylene groups, respectively) were prepared and the effect of spacer length on adhesion and expansion of umbilical cord blood hematopoietic stem/progenitor cells (HSPCs) was investigated.Materials and Methods. Electrospun polymer nanofiber scaffolds were functionalized with poly(acrylic acid) grafting, followed by conjugation of amino groups with different spacers. HSPCs were expanded on aminated scaffolds for 10 days. Cell proliferation, surface marker expression, clonogenic potential, and nonobese diabetic (NOD)/severe combined immunodeficient (SCID) repopulation potential of the expanded cells were evaluated following expansion culture.Results. Aminated nanofiber scaffolds with ethylene and butylene spacers showed high-expansion efficiencies (773- and 805-fold expansion of total cells, 200- and 235-fold expansion of CD34(+)CD45(+) cells, respectively). HSPC proliferation on aminated scaffold with hexylene spacer was significantly lower (210-fold expansion of total cells and 86-fold expansion of CD34(+)CD45(+) cells), but maintained the highest CD34(+)CD45(+) cell fraction (41.1%). Colony-forming unit granulocyte-erythrocyte-monocyte-megakaryocyte and long-term culture-initiating cell maintenance was similar for HSPCs expanded on all three aminated nanofiber scaffolds; nevertheless, the NOD/SCID mice engraftment potential of HSPCs expanded on aminoethyl and aminobutyl conjugated nanofibers was significantly higher than that on aminohexyl conjugated nanofibers.Conclusion. This study demonstrated that aminated nanofibers are superior substrates for ex vivo HSPC expansion, which was correlated with the enhanced HSPC adhesion to these aminated nanofibers. The spacer, through which amino groups were conjugated to nanofiber surface, affected the expansion outcome. Our results highlighted the importance of scaffold topography and cell-substrate interaction to regulating HSPC proliferation and self-renewal in cytokine-supplemented expansion. (c) 2007 International Society for Experimental Hematology. Published by Elsevier Inc.