CAREER: Biomechanical Regulation of Mesenchymal Stem Cell Differentiation

职业：间充质干细胞分化的生物力学调节

• 批准号: 2143151
• 负责人: Shue Wang
• 金额: $ 55.85万
• 依托单位: University of New Haven
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-05-01 至 2027-04-30
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2143151&HistoricalAwards=false
• 关键词: CAREER; Biomechanical; Regulation; Mesenchymal; Stem

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.

该教师早期职业发展计划（职业）奖将支持研究，以研究如何调节间充质干细胞分化。 间充质干细胞具有自我更新特性。 这些细胞在基于细胞的组织工程和再生医学方面具有很大的潜力。 然而，间充质干细胞如何分化使形成的细胞的基本机制仍然很熟悉。 该项目将系统地研究影响分化的生物物理和生化因素的相互作用。 这项工作将使用一个新型的微型工程平台来确定影响间质干细胞分化的功能和机制。 教育活动将为广泛的受众提供以目标为基础的，基于项目的，动手学习的经验，重点是女性和代表性不足的少数群体。 本科生和研究生将通过基于项目的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，并增强K-12学生参与STEM教育。 通过提高对间充质干细胞分化的基本了解，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。该项目的具体研究目标是确定机械敏感的非编码RNA在调节成骨分化中的功能和机制。 总体重点是使用一种新型的多重纳米传感器，2D和3D培养系统来研究间充质干细胞分化过程中刚度，几何引导和牵引力如何调节非编码RNA。 这将通过三个研究目标实现。 第一个目标是开发和表征单个细胞水平的非编码RNA检测的新型多重纳米传感器。 第二个目标是阐明非编码RNA及其与组织，细胞和分子水平的生物物理因子的串扰的机械敏感作用。 最终目标是研究3D微环境中成骨分化过程中非编码RNA的机械调节。 该项目的完成将提供有关响应生物物理因素的非编码RNA基础机制的新信息和见解。 从这些实验中获得的知识将为基于细胞的疗法的应用机制分化的基本原理提供新的见解，这将支持生物制造和组织工程系统的发展。该奖项反映了NSF的法定任务，并通过使用基金会的智力效果进行评估，并通过评估了基金会和广泛的影响。

项目成果

Long non-coding RNA (lncRNA) MALAT1 in regulating osteogenic and adipogenic differentiation using a double-stranded gapmer locked nucleic acid nanobiosensor

使用双链间隙体锁定核酸纳米生物传感器调节长非编码RNA (lncRNA) MALAT1 成骨和脂肪形成分化

• DOI: 10.1039/d3an01531a
• 发表时间: 2023
• 期刊: The Analyst
• 作者: Fasciano, Samantha;Luo, Shuai;Wang, Shue
• 通讯作者: Wang, Shue

Detection of MicroRNA Expression Dynamics Using LNA/DNA Nanobiosensor

使用 LNA/DNA 纳米生物传感器检测 MicroRNA 表达动态

• 发表时间: 2023
• 期刊: Methods in molecular biology
• 作者: Yuwen Zhao, Shue Wang

Recent advances of droplet-based microfluidics for engineering artificial cells

• DOI: 10.1016/j.slast.2023.05.002
• 发表时间: 2024-04-06
• 期刊: SLAS TECHNOLOGY
• 影响因子: 2.7
• 作者: Fasciano，Samantha;Wang，Shue
• 通讯作者: Wang，Shue