Efficient magnetic enrichment of antigen-specific T cells by engineering particle properties.
Efficient magnetic enrichment of antigen-specific T cells by engineering particle properties.
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DOI：
10.1016/j.biomaterials.2018.09.029
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发表时间：
2018-12
期刊：
影响因子：
14
通讯作者：
Schneck JP
中科院分区：
文献类型：
--
作者：
Hickey JW;Isser AY;Vicente FP;Warner SB;Mao HQ;Schneck JP
磁性颗粒可以丰富所需的细胞群，以帮助了解细胞类型的功能和机制、诊断和治疗。由于细胞在配体类型、位置、表达和密度上是不同的，因此有必要仔细考虑用于正隔离的磁粉设计。抗原特异性免疫细胞的频率很低，这使得研究、鉴定和利用这些细胞进行治疗是一个挑战。在这里，我们论证了基于T细胞生物学的磁粉设计的重要性。我们创造了识别稀有抗原特异性T细胞的磁性颗粒，并定量研究了重要的颗粒属性，包括大小、浓度、配基密度和富含这些稀有细胞的配基选择。我们观察到颗粒参数之间的竞争最优，300纳米颗粒与高密度的抗原特异性配体一起功能化，实现了最高的靶细胞浓缩和回收率。在丰富并激活内源性反应的过程中，300 nm的aAPC产生近65%的抗原特异性T细胞，内源性前体细胞至少扩增450倍，仅7天后抗原特异性细胞的数量增加5倍。本系统地研究了磁性富集物中的颗粒特性，为通过生物配体分离稀有细胞的颗粒工程设计原理提供了一个案例研究。
Magnetic particles can enrich desired cell populations to aid in understanding cell-type functions and mechanisms, diagnosis, and therapy. As cells are heterogeneous in ligand type, location, expression, and density, careful consideration of magnetic particle design for positive isolation is necessary. Antigen-specific immune cells have low frequencies, which has made studying, identifying, and utilizing these cells for therapy a challenge. Here we demonstrate the importance of magnetic particle design based on the biology of T cells. We create magnetic particles which recognize rare antigen-specific T cells and quantitatively investigate important particle properties including size, concentration, ligand density, and ligand choice in enriching these rare cells. We observe competing optima among particle parameters, with 300 nm particles functionalized with a high density of antigen-specific ligand achieving the highest enrichment and recovery of target cells. In enriching and then activating an endogenous response, 300 nm aAPCs generate nearly 65% antigen-specific T cells with at least 450-fold expansion from endogenous precursors and a 5-fold increase in numbers of antigen-specific cells after only seven days. This systematic study of particle properties in magnetic enrichment provides a case study for the engineering design principles of particles for the isolation of rare cells through biological ligands.
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影响因子：
15.9
作者：
Berger, Carolina;Jensen, Michael C.;Riddell, Stanley R.
通讯作者：
Riddell, Stanley R.
DOI：
10.1016/j.jconrel.2015.10.006
发表时间：
2015-12-10
期刊：
Journal of controlled release : official journal of the Controlled Release Society
影响因子：
--
作者：
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影响因子：
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作者：
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通讯作者：
Spatz JP
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影响因子：
32.4
作者：
Martínez-Martín N;Fernández-Arenas E;Cemerski S;Delgado P;Turner M;Heuser J;Irvine DJ;Huang B;Bustelo XR;Shaw A;Alarcón B
通讯作者：
Alarcón B
DOI：
10.1084/jem.20070784
发表时间：
2007-10-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
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Appay V