CAREER: Engineering MSC Progenitors using Dielectrophoresis for Better Cell Therapies

间充质干细胞（MSCs）在体内起着自我修复系统的作用。MSC具有独特的能力，可以转变成各种不同的细胞，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。由于这些好处，间充质干细胞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，因为间充质干细胞通常以细胞类型的混合物存在。在这个项目中，微流控技术被提议根据与促进愈合的MSCs相关的关键电参数来选择细胞。该项目包括努力增加攻读STEM领域的非裔美国本科生和高中生的数量。间充质干细胞培养包括干细胞、部分分化祖细胞和完全分化细胞。由于无法选择特定的细胞亚群，MSC的治疗潜力受到限制。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。第一种是利用无标记细胞分选技术，即介电电泳，根据其功能靶向间充质祖细胞。第二是扩大可用于可靠地鉴定MSC祖细胞的生物标志物的数量。第三是查明细胞极化的关键结构和分子贡献。该项目将尝试扩大独立生物标志物的数量，这些生物标志物可用于基于膜电容和细胞质电导率的细胞选择。这些研究的成功完成将对细胞表面分子调控分化、细胞信号分子释放和间充质谱系中的基因表达产生新的分子见解。此外，我们将有一个有效的介电基微流控装置用于干细胞分选，以推进生物制造的努力，以获得更好的细胞治疗。该奖项反映了美国国家科学基金会的法定使命，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。

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.