CAREER: Understanding the Effects of Mechanical Dosing on Mesenchymal Stem Cell Identity

这项学院早期职业发展(Career)基金将研究干细胞的“身份”如何通过其周围材料的机械特性来保存。干细胞的特性由其分裂、适应和分化的能力来定义。这项工作将集中在间充质干细胞上，这是一种成体干细胞，通常来自骨髓，并通过组织培养技术进行扩增。控制间充质干细胞的特性对于细胞制造和再生医学非常重要。该项目的研究目标是通过开发具有可独立控制的刚性、粘附性和细胞-细胞信号特性的材料来克服目前间充质干细胞细胞培养环境中的局限性。该项目的教育目标是将研究与正在进行的教育活动相结合，以提高科学素养和公平。这项工作将包括让未被充分代表的高中生和本科生进行面对面的暑期研究，并参加虚拟互动模块，这些模块旨在灌输对细胞生物学和材料科学的热情。这项研究的中心假设是，可以利用机械给药策略来控制间充质干细胞的增殖、对动态材料的适应以及3D水凝胶中的分化。这一假说将通过：(I)确定在体外扩增过程中基质机械传感对间充质干细胞增殖和干性的意义，(Ii)阐明粘合剂和细胞-细胞模拟肽在间充质干细胞机械适应中的作用，以及(Iii)确定在3D可注射水凝胶中提高间充质干细胞分化潜力的机械给药参数。从这些研究中获得的基本知识有望导致当前间充质干细胞培养环境的范式转变，并在细胞制造、干细胞机械生物学和再生医学方面取得重大进展。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。

This Faculty Early Career Development (CAREER) grant will study how the “identity” of stem cells can be preserved by the mechanical properties of the materials that surround them. Stem cell identity is defined by their ability to divide, adapt, and differentiate. This work will focus on mesenchymal stem cells, which are adult stem cells typically sourced from bone marrow and expanded with tissue culture techniques. Controlling mesenchymal stem cell identity is important for cell manufacturing and regenerative medicine. The research goal of this project is to overcome current limitations in the cell culture environment of mesenchymal stem cells by developing materials with independently controllable properties of stiffness, adhesion, and cell-cell signaling. The educational goal of this project is to integrate research with ongoing educational activities to increase scientific literacy and equity. The work will involve programs for underrepresented high school and undergraduate students to conduct in-person summer research and attend virtual interactive modules designed to instill a passion for cell biology and materials science.The central hypothesis of this research is that mechanical dosing strategies can be leveraged to control mesenchymal stem cell proliferation, adaptation to dynamic materials, and differentiation within 3D hydrogels. This hypothesis will be tested by: (i) determining the significance of matrix mechanosensing during in vitro expansion on mesenchymal stem cell proliferation and stemness, (ii) elucidating the role of adhesive and cell-cell mimetic peptides on mesenchymal stem cell mechanical adaptation, and (iii) identifying mechanical dosing parameters that increase the differentiation potential of mesenchymal stem cells in 3D injectable hydrogels. The fundamental knowledge gained from these studies is expected to lead to a paradigm shift in current mesenchymal stem cell culture environments and result in significant advances in cell manufacturing, stem cell mechanobiology, and regenerative medicine.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.