CAREER: Biomechanical Regulation of Mesenchymal Stem Cell Differentiation

这个教师早期职业发展计划（Career）奖将支持研究间充质干细胞分化是如何被调节的。间充质干细胞具有自我更新的特性。这些细胞在组织工程和再生医学的细胞治疗中具有巨大的潜力。然而，间充质干细胞如何分化成形成细胞的基本机制仍然知之甚少。本项目将系统研究影响分化的生物物理和生化因素之间的相互作用。这项工作将使用一个新的微工程平台来确定影响间充质干细胞分化的功能和机制。教育活动将向广大受众提供面向目标、以项目为基础的实践学习经验，重点是妇女和代表性不足的少数民族。本科生和研究生将通过项目课程和研究机会进行培训。此外，夏季外展活动将提高教师对STEM职业的认识，并提高K-12学生对STEM教育的参与度。通过提高对间充质干细胞分化的基本理解，该项目将支持生物制造和组织工程系统的发展，以产生正常器官功能所必需的特定干细胞谱系。本项目的具体研究目标是明确机械敏感性非编码rna在调控成骨分化中的功能和机制。总体重点是研究刚度、几何导向和牵引力如何在间充质干细胞分化过程中调节非编码rna，使用一种新型的多重纳米生物传感器、2D和3D培养系统。这将通过三个研究目标来完成。第一个目标是开发和表征一种新型的多路纳米生物传感器，用于在单细胞水平上检测非编码rna。第二个目标是阐明非编码rna的机械敏感作用及其在组织、细胞和分子水平上与生物物理因子的串扰。最终目的是研究非编码rna在三维微环境成骨分化过程中的机制调控。该项目的完成将为非编码rna响应生物物理因素的机制提供新的信息和见解。从这些实验中获得的知识将为细胞治疗的应用提供对成骨分化机制调节的基本原理的新见解，这将支持生物制造和组织工程系统的进步。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。

This Faculty Early Career Development Program (CAREER) award will support research to study the how mesenchymal stem cell differentiation is regulated. Mesenchymal stem cells have self-renewal properties. These cells have great potential in cell-based therapies for tissue engineering and regenerative medicine. However, the fundamental mechanisms of how mesenchymal stem cells differentiate into cells that make formation remains poorly understood. This project will systematically study the interactions of biophysical and biochemical factors that affect differentiation. This work will use a novel micro-engineered platform to identify the functions and mechanisms that influence mesenchymal stem cell differentiation. The educational activities will provide a goal-oriented, project-based, hands-on learning experience to a broad audience, with an emphasis on women and underrepresented minorities. Undergraduate and graduate students will be trained through project-based courses and research opportunities. In addition, summer outreach activities will increase teachers' awareness of STEM careers and enhance the engagement of K-12 students into STEM education. By improving the fundamental understanding of mesenchymal stem cell differentiation, this project will support the development of biomanufacturing and tissue engineering systems to produce specific stem cell lineage that are necessary for normal organ function. The specific research goal of this project is to identify the function and mechanisms of mechanosensitive non-coding RNAs in regulating osteogenic differentiation. The overarching focus is to investigate how stiffness, geometric guidance, and traction force regulate non-coding RNAs during mesenchymal stem cell differentiation, using a novel multiplex nanobiosensor, 2D and 3D culture systems. This will be accomplished through three research objectives. The first objective is to develop and characterize a novel multiplex nanobiosensor for non-coding RNAs detection at the single cell level. The second objective is to elucidate the mechanosensitive role of non-coding RNAs and their crosstalk with biophysical factors at the tissue, cell, and molecular level. The final objective is to investigate the mechanoregulation of non-coding RNAs during osteogenic differentiation in 3D microenvironments. Completion of this project will provide novel information and insights regarding the mechanisms underlying non-coding RNAs in response to biophysical factors. The knowledge gained from these experiments will provide new insights into the fundamental principles of mechanoregulation of osteogenic differentiation for the application of cell-based therapies, which will support the advancement of the biomanufacturing and tissue engineering systems.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.