Bioactive Materials for Stem Cell Control

描述(申请人提供)：体内干细胞存在于一个复杂的微环境中，提供给它们许多信号因子来调节它们的行为和功能，了解这些因素如何影响干细胞的命运是细胞和发育生物学的主要挑战。因此，设计控制细胞行为的策略对于干细胞生物学从发育到成年期的基础研究以及干细胞在组织工程和再生中的应用都是至关重要的。这项提议的目标是设计新的生物材料来调节和控制干细胞的行为。具体地说，这些定义明确的仿生配体和表面将控制调节神经干细胞(NSCs)分化或增殖的信号通路的激活。我们选择神经干细胞作为一种有效的细胞系统来研究干细胞控制的基本生物学机制，探索其生物医学潜力，并评估生物-合成杂化材料在控制干细胞在培养中的多种功能方面的前景。NSC丝裂原Sonic Hedgehog和Notch配体Delta将被嫁接到可溶性脂质体和合成表面上，以调节细胞的增殖和分化。这项提案将探索这些合成细胞效应器的结构-活性关系。效应器的效价、尺寸、流动性和剂量对受体聚集、信号转导、细胞增殖和细胞分化的影响将被研究。我们的具体目标是：1.确定显示Sonic Hedgehog或Delta的合成可溶性脂质体是否能够控制NSC的功能。2.分析用Sonic Hedgehog或Delta对仿生表面进行功能化处理是否能有效地调节NSC的行为。

DESCRIPTION (provided by applicant): Stem cells in vivo reside in a complex microenvironment that presents them with numerous signaling factors that regulate their behavior and functions, and understanding how these factors influence stem cell fate is a major challenge of cell and developmental biology. Designing strategies to control cell behavior is therefore critical for both fundamental studies of stem cell biology from development through adulthood, as well as for applications of stem cells in tissue engineering and regeneration. The objective of this proposal is to design novel biomaterials that modulate and control stem cell behavior. Specifically, these well-defined, biomimetic ligands and surfaces will control the activation of signaling pathways that regulate the differentiation or proliferation of neural stem cells (NSCs). We have chosen NSCs as an effective cellular system to investigate the basic biological mechanisms of stem cell control, to explore their biomedical potential, and to evaluate the promise of hybrid biological-synthetic materials for controlling the multitude functions of a stem cell in culture. The NSC mitogen Sonic hedgehog and the Notch ligand Delta will be grafted onto both soluble liposomes and synthetic surfaces to modulate cell proliferation and differentiation. This proposal will explore the structure-activity relationships of these synthetic cellular effectors. The effects of effector valency, dimensions, fluidity, and dosage on receptor clustering, signal transduction, cell proliferation, and cell differentiation will be studied. Our Specific Aims are: 1. To determine whether synthetic soluble liposome constructs displaying Sonic hedgehog or Delta can control NSC function. 2. To analyze whether biomimetic surfaces functionalized with Sonic hedgehog or Delta can effectively regulate NSC behavior.