UNS: Nanotopographical Memory Modulates Stem Cell Fate

1511759Yang， Yong传统的细胞培养方法使用平坦、坚硬的塑料表面，并不能再现细胞在体内与细胞相互作用的细胞外基质（ECM）的特征（例如，刚度和纳米形貌）。因此，细胞在这些表面上的行为明显偏离它们在体内的对应体。迫切需要将ECM特性纳入干细胞培养技术。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/底物纳米形貌和刚度在体内对许多发育、生理和病理过程具有重要影响，并且在体外对细胞行为和干细胞命运决定具有深远影响。假设干细胞可以保留过去培养环境中的纳米形貌信息，并且纳米形貌记忆可以影响干细胞未来命运的决定。本研究的目的是验证这一假设，并描述纳米形貌记忆效应的潜在机制。本文提出以人间充质干细胞（hMSCs）为模型细胞研究纳米形貌记忆效应的三个研究目标：(1)利用纳米形貌调节yes相关蛋白（YAP）在细胞内的定位；(2)验证纳米形貌记忆效应；(3)阐明纳米形貌记忆效应的潜在机制。本研究将促进对发育和病理过程中细胞机械转导和干细胞可塑性的理解。这将引起人们对体外培养过程中意想不到的纳米形貌记忆效应的关注，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，并为再生医学中植入物和医疗器械的新型生物材料和细胞-基质界面的设计提供见解。此外，将建立一个协作的、跨学科的、通过研究学习的系统，为促进西弗吉尼亚州的纳米生物技术教育提供基础设施。该奖项由CBET生物技术与生化工程项目颁发，由材料研究部生物材料项目共同资助。

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.