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.

间充质干细胞（MSC）作为体内的自我修复系统，具有转变为各种不同细胞的独特能力，并且它们可以根据身体的需要释放细胞信号分子来支持我们的免疫系统。为了实现这些优势，间充质干细胞的生物制造已成为一个重要的研究领域。然而，由于间充质干细胞通常以多种细胞类型的混合物形式存在，因此获得具有特定功能的细胞很困难。在该项目中，提出了微流体技术。根据与促进愈合的 MSC 相关的关键电参数来选择细胞。该项目包括努力增加追求 STEM 领域的非洲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MSC 的治疗潜力因无法选择特定的细胞亚群而受到限制。该项目有 3 个目标。第二个是扩大可用于可靠识别 MSC 祖细胞的生物标志物的数量，第三个是查明对细胞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。此外，我们还将拥有一种有效的基于介电电泳的微流体装置，用于干细胞分选，以推进生物制造工作，以实现更好的细胞治疗。通过使用基金会的智力价值和更广泛的影响审查标准进行评估，NSF 的法定使命被认为值得支持。

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: 2023-06
• 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.