Stem cell enrichment with selectin receptors: mimicking the pH environment of trauma.

Stem cell enrichment with selectin receptors: mimicking the pH environment of trauma.
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DOI:
10.3390/s130912516
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发表时间:
2013-09-17
期刊:
Sensors (Basel, Switzerland)
影响因子:
--
通讯作者:
King MR
King MR
中科院分区:
其他
文献类型:
--
作者:
Cao TM;Mitchell MJ;Liesveld J;King MR

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造血干细胞和祖细胞(HSPC)的分离对于移植治疗和HSPC研究是至关重要的,然而目前的分离技术昂贵、耗时且结果多变。选择素包被的微管在从人骨髓中快速分离HSPC方面显示出了希望,但进一步纯化HSPC仍然是一个挑战。因此,我们提出了一种仿生的HSPC分离装置,以模拟创伤时的酸性血管微环境,从而提高L-选择素与其拮抗受体PSGL-1与HSPC的结合频率。在酸性pH条件下,L-选择素包裹的微管增强了CD34+HSPC的粘附性,表现为细胞滚动速度的降低和滚动通量的增加。动态光散射被用作一种新的传感器来证实L-选择素在酸性条件下的构象变化,正如先前分子动力学预测的那样。这些结果表明,模拟创伤的酸性条件可以诱导L-选择素的构象延长,这可以用于临床上基于流动的HSPC分离。
The isolation of hematopoietic stem and progenitor cells (HSPCs) is critical for transplantation therapy and HSPC research, however current isolation techniques can be prohibitively expensive, time-consuming, and produce variable results. Selectin-coated microtubes have shown promise in rapidly isolating HSPCs from human bone marrow, but further purification of HSPCs remains a challenge. Herein, a biomimetic device for HSPC isolation is presented to mimic the acidic vascular microenvironment during trauma, which can enhance the binding frequency between L-selectin and its counter-receptor PSGL-1 and HSPCs. Under acidic pH conditions, L-selectin coated microtubes enhanced CD34+ HSPC adhesion, as evidenced by decreased cell rolling velocity and increased rolling flux. Dynamic light scattering was utilized as a novel sensor to confirm an L-selectin conformational change under acidic conditions, as previously predicted by molecular dynamics. These results suggest that mimicking the acidic conditions of trauma can induce a conformational extension of L-selectin, which can be utilized for flow-based, clinical isolation of HSPCs.
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