Microenvironmental Regulation of Oval Cell Functions

描述（由申请人提供）：肝卵圆细胞是肝组织工程和其他基于细胞的肝脏治疗的一个有趣的潜在细胞来源，因为它们能够在培养中扩增，并具有向肝细胞或胆管上皮细胞的双潜能分化。然而，卵形细胞生物学的许多方面，特别是微环境因素对卵形细胞反应的调节，仍然不清楚。提出的研究将利用基于光聚合水凝胶的模型系统来研究2-D和3-D设置下的卵圆细胞功能。具体来说，这些实验将研究整合素和Notch受体在指定卵圆细胞命运过程中的作用，如粘附、迁移和信号传导。光图案水凝胶平台将用于研究外部信号不对称呈现的影响，整合素和Notch之间的串扰也将被评估。这些研究将提供对卵形细胞反应的基本见解，对组织工程肝脏治疗的发展至关重要。以3-D和/或不对称的方式控制卵形细胞功能的重要调节因子的结合代表了卵形细胞为基础的组织工程肝脏结构的重要进展。

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.