CAREER: Engineering MSC Progenitors using Dielectrophoresis for Better Cell Therapies

间充质干细胞在体内起着自我修复系统的作用。骨髓间充质干细胞具有转变为各种不同细胞的独特能力，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，骨髓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，获得具有特定功能的细胞是困难的，因为MSCs通常是以多种细胞类型的混合物存在的。在这个项目中，微流控技术被提出根据与促进愈合的MSCs相关的关键电参数来选择细胞。该项目包括努力增加从事STEM领域的非裔美国本科生和高中生的数量。MSC培养包含干细胞、部分分化的祖细胞和完全分化的细胞。由于不能选择特定的细胞亚群，MSC的治疗潜力受到限制。关于细胞群体中所有MSC前体亚型的定义特征和功能能力，人们知之甚少。这个项目有3个目标。第一种是使用一种无标记细胞分选技术，即介电泳法，根据MSC祖细胞的功能将其作为靶标。第二是扩大可用于可靠识别MSC前体细胞的生物标志物的数量。第三是确定对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膜电容和细胞质电导的细胞选择的独立生物标记物的数量。这些研究的成功完成将对细胞表面分子调节分化、细胞信号分子的释放以及间充质系中的基因表达产生新的分子见解。此外，我们将拥有一种有效的基于介电泳法的微流控设备，用于干细胞分离，以促进更好的细胞疗法的生物制造努力。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势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.