CAREER: Engineering MSC Progenitors using Dielectrophoresis for Better Cell Therapies

职业：使用介电泳工程 MSC 祖细胞以获得更好的细胞疗法

• 批准号: 2048221
• 负责人: Tayloria Adams
• 金额: $ 50万
• 依托单位: University of California-Irvine
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-02-01 至 2026-01-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2048221&HistoricalAwards=false
• 关键词: CAREER; Engineering; MSC; Progenitors; using

Mesenchymal stem cells (MSCs) act as a self-repair system in the body. MSC's have the unique ability to change into a variety of different cells, and they can support our immune system by releasing cell signaling molecules depending on the body’s needs. Due to these benefits, biomanufacturing of MSCs has emerged as a vital area of research. However, obtaining cells that exhibit specific functions is difficult because MSCs typically exist as a mixture of cell types. In this project, microfluidic technology is proposed to select cells based on key electrical parameters that have been associated with MSCs that promote healing. This project includes efforts to increase the number of African American undergraduate and high school students pursuing STEM fields.MSC cultures contain stem cells, partially differentiated progenitor cells, and fully differentiated cells. MSC therapeutic potential is limited by the inability to select specific cell subpopulations. Little is known about the defining characteristics and functional capabilities of all MSC progenitor subtypes within a cell population. This project has 3 goals. The first is to use a label- free cell sorting technique, dielectrophoresis, to target MSC progenitors based on their functionality. The second is to expand the number of biomarkers that can be used to reliably identify MSC progenitors. The third is to pinpoint the key structural and molecular contributions to cell polarization. This project will attempt to expand the number of independent biomarkers that can be used for cell selection with dielectrophoresis based membrane capacitance and cytoplasm conductivity. The successful completion of these investigations will yield new molecular insights into cell surface molecules regulating differentiation, the release of cell signaling molecules, and gene expression in the mesenchymal lineage. Additionally, we will have an effective dielectrophoresis-based microfluidic device for stem cell sorting to advance biomanufacturing efforts for better cell therapies.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

骨髓间充质干细胞（MSC）在体内充当自我修复系统。MSC具有转变成各种不同细胞的独特能力，它们可以根据身体的需要通过释放细胞信号分子来支持我们的免疫系统。由于这些好处，MSC的生物制造已经成为一个重要的研究领域。然而，获得表现出特定功能的细胞是困难的，因为MSC通常作为细胞类型的混合物存在。在这个项目中，微流体技术被提出来选择细胞的基础上，已与促进愈合的骨髓间充质干细胞相关的关键电参数。该项目包括努力增加追求STEM领域的非裔美国本科生和高中生的数量。MSC培养物含有干细胞，部分分化的祖细胞和完全分化的细胞。MSC的治疗潜力受到无法选择特定细胞亚群的限制。对于细胞群中所有MSC祖细胞亚型的定义特征和功能能力知之甚少。这个项目有三个目标。第一种是使用无标记的细胞分选技术，介电泳，基于MSC祖细胞的功能靶向MSC祖细胞。第二是扩大可用于可靠鉴定MSC祖细胞的生物标志物的数量。 第三是确定细胞极化的关键结构和分子贡献。该项目将尝试扩大可用于基于介电泳的膜电容和细胞质电导率的细胞选择的独立生物标志物的数量。这些研究的成功完成将产生新的分子见解调节分化的细胞表面分子，细胞信号分子的释放，和间充质谱系中的基因表达。此外，我们将拥有一个有效的基于微流控芯片的干细胞分选装置，以推进生物制造工作，实现更好的细胞治疗。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

项目成果

Light-Induced Dielectrophoresis for Characterizing the Electrical Behavior of Human Mesenchymal Stem Cells

光诱导介电电泳用于表征人类间充质干细胞的电行为

• DOI: 10.3791/64909
• 发表时间: 2023
• 期刊: Journal of Visualized Experiments
• 作者: Lacy, Kiara L.;Salib, Samuel;Tran, Mary;Tsai, Tunglin;Valentine, Rominna;Ardoña, Herdeline Ann;Adams, Tayloria N.
• 通讯作者: Adams, Tayloria N.