Microenvironmental Regulation of Oval Cell Functions

卵圆细胞功能的微环境调节

基本信息

批准号：
7132121
负责人：
Gregory H Underhill
金额：
$ 5.04万
依托单位：
MASSACHUSETTS INSTITUTE OF TECHNOLOGY
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-07-01 至 2007-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7132121
关键词：
bioengineering /biomedical engineering biological signal transduction biomaterials cell adhesion cell component structure /function cell migration flow cytometry gel integrins liver cells polymerization postdoctoral investigator stem cells tissue engineering

项目摘要

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.

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种有趣的潜在细胞来源，因为它们能够在培养物中扩增并且具有双能分化为肝细胞或胆管上皮细胞的能力。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，仍不清楚。拟议的研究将利用基于光聚合水凝胶的模型系统来研究 2D 和 3D 设置中的卵圆细胞功能。具体来说，这些实验将检查整合素和Notch受体在指定卵圆细胞命运过程（例如粘附、迁移和信号传导）中的作用。光图案水凝胶平台将用于研究外部线索的不对称呈现的影响，并且还将评估整合素和Notch之间的串扰。这些研究将为卵圆细胞反应提供基本见解，这对于组织工程肝脏疗法的发展非常重要。以 3D 和/或不对称方式控制卵圆细胞功能重要调节因子的掺入代表了基于卵圆细胞的组织工程肝脏构建的重要进展。