Microenvironmental Regulation of Oval Cell Functions

卵圆细胞功能的微环境调节

• 批准号: 6884513
• 负责人: Gregory H Underhill
• 金额: $ 4.83万
• 依托单位: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 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/6884513
• 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

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，并且具有向肝细胞或胆管上皮细胞分化的双能性。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，仍然不确定。拟议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设置中的卵圆细胞功能。具体而言，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中的作用，如粘附，迁移和信号传导。将利用光图案化的水凝胶平台来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的见解，这对组织工程肝脏治疗的发展很重要。卵圆细胞功能的重要调节因子在3-D和/或不对称中的受控掺入代表了朝向基于卵圆细胞的组织工程化肝脏构建体的重要进展。