Microenvironmental Regulation of Oval Cell Functions

描述(申请人提供)：肝卵圆细胞是一个有趣的潜在细胞来源的肝脏组织工程和其他基于细胞的治疗，因为它们的能力，在培养和双向分化为肝细胞或胆管上皮细胞。然而，卵圆细胞生物学的许多方面，特别是微环境因素对卵圆细胞反应的调节，仍然没有明确的定义。这项拟议的研究将利用基于光聚合水凝胶的模型系统来研究椭圆形细胞在二维和三维环境中的功能。具体地说，这些实验将研究整合素和Notch受体在指定椭圆形细胞命运过程中的作用，如黏附、迁移和信号传递。将利用光特性水凝胶平台来研究外部提示的不对称呈现的影响，并将评估整合素和Notch之间的串扰。这些研究将提供对卵圆细胞反应的基本见解，这对组织工程肝病治疗的发展很重要。在三维和/或不对称的情况下，受控地整合卵圆细胞功能的重要调节因子，代表着向基于椭圆形细胞的组织工程肝脏构建的重要进展。

DESCRIPTION (provided by applicant): Hepatic oval cells are an intriguing potential cell source for liver tissue engineering and other cell-based liver therapies due to their ability to be expanded in culture and their bipotential differentiation into hepatocytes or bile duct epithelial cells. However, many aspects of oval cell bjology, in particular, the regulation of oval cell responses by microenvironmental factors, remain undefined. The proposed research will utilize a model system based on photopolymerized hydrogels to investigate oval cell functions in 2-D and 3-D settings. Specifically, these experiments will examine the role of integrins and Notch receptors in specifying oval cell fate processes such as adhesion, migration, and signaling. Photopatterned hydrogel platforms will be utilized to investigate the effect of asymmetric presentation of external cues, and cross-talk between integrins and Notch will also be assessed. These studies will provide fundamental insight into oval cell responses, important for the development of tissue engineered liver therapies. The controlled incorporation of important regulators of oval cell functions in 3-D and/or asymmetrically represents an important advancement towards an oval cell-based tissue engineered liver construct.