UNS: Nanotopographical Memory Modulates Stem Cell Fate

UNS：纳米地形记忆调节干细胞命运

• 批准号: 1511759
• 负责人: Yong Yang
• 金额: $ 35.09万
• 依托单位: West Virginia University Research Corporation
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-07-01 至 2018-03-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1511759&HistoricalAwards=false
• 关键词: UNS; Nanotopographical; Memory; Modulates; Stem

1511759Yang, Yong Conventional cell culture methods using flat, stiff plastic surfaces do not recapitulate characteristics (e.g., stiffness and nanotopography) of the extracellular matrix (ECM) with which cells interact in vivo. Therefore, cell behavior on such surfaces significantly deviate from their in vivo counterparts. There is a pressing need to incorporate the ECM characteristics into stem cell culture technologies. The goal of this research is to advance next-generation cell culture technologies by investigating nanotopographical memory effects of stem cells.ECM/substrate nanotopography and stiffness critically influence numerous developmental, physiological and pathological processes in vivo, and have a profound influence on cell behavior and stem cell fate decision in vitro. It is hypothesized that stem cells can retain nanotopographical information from past culture environments and the nanotopographical memory can influence future fate decision of stem cells. The objective of the proposed research is to test this hypothesis and to delineate the underlying mechanism of nanotopographical memory effects. Three research objectives using human mesenchymal stem cells (hMSCs) as model cells are proposed to study the nanotopographical memory effects: (1) Regulate Yes-associated protein (YAP) intracellular localization by using nanotopography, (2) Validate nanotopographical memory effects, and (3) Delineate the underlying mechanism of nanotopographical memory effects. This research will advance the understanding of cellular mechanotransduction and stem cell plasticity during developmental and pathological processes. It will call attention to unintended nanotopographical memory effects during in vitro culture, which may affect stem cell function and differentiation. This research will contribute to the development of next-generation stem cell culture technologies, and provide insight into the design of new biomaterials and the cell-substrate interfaces of implants and medical devices for regenerative medicine. In addition, a collaborative, cross-disciplinary, learn-through-research system will be established to provide the basic infrastructure to promote nanobiotechnology education in West Virginia.This award by the Biotechnology and Biochemical Engineering Program of CBET is co-funded by the Biomaterials Program of the Division of Materials Research.

1511759Yang, Yong 使用平坦、坚硬的塑料表面的传统细胞培养方法不能概括细胞在体内相互作用的细胞外基质 (ECM) 的特征（例如硬度和纳米形貌）。 因此，此类表面上的细胞行为与其体内对应物显着不同。迫切需要将 ECM 特性融入干细胞培养技术中。本研究的目标是通过研究干细胞的纳米形貌记忆效应来推进下一代细胞培养技术。ECM/基质纳米形貌和硬度对体内众多发育、生理和病理过程产生至关重要的影响，并对细胞行为和行为产生深远影响。体外干细胞命运决定。 据推测，干细胞可以保留过去培养环境中的纳米地形信息，并且纳米地形记忆可以影响干细胞未来的命运决定。本研究的目的是检验这一假设并描述纳米地形记忆效应的潜在机制。提出使用人间充质干细胞（hMSC）作为模型细胞来研究纳米拓扑记忆效应的三个研究目标：（1）利用纳米拓扑调节Yes相关蛋白（YAP）的细胞内定位，（2）验证纳米拓扑记忆效应，以及（ 3）描述纳米拓扑记忆效应的潜在机制。这项研究将增进对发育和病理过程中细胞力转导和干细胞可塑性的理解。它将引起人们对体外培养过程中意想不到的纳米拓扑记忆效应的关注，这可能会影响干细胞的功能和分化。这项研究将有助于下一代干细胞培养技术的发展，并为再生医学的新型生物材料以及植入物和医疗设备的细胞-基质界面的设计提供见解。此外，还将建立一个协作的、跨学科的、边学边学的系统，为西弗吉尼亚州促进纳米生物技术教育提供基础设施。该奖项由CBET生物技术和生化工程项目、生物材料学院共同资助材料研究部的计划。