Bioactive Materials for Stem Cell Control

描述（由申请人提供）：干细胞在体内存在于复杂的微环境中，该微环境为干细胞提供了许多调节其行为和功能的信号传导因子，并且理解这些因子如何影响干细胞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从发育到成年的干细胞生物学基础研究以及干细胞在组织工程和再生中的应用都至关重要。本提案的目的是设计新型生物材料，调节和控制干细胞的行为。具体而言，这些明确定义的仿生配体和表面将控制调节神经干细胞（NSC）的分化或增殖的信号传导途径的激活。我们选择神经干细胞作为一种有效的细胞系统，以研究干细胞控制的基本生物学机制，探索其生物医学潜力，并评估混合生物合成材料用于控制培养中干细胞的多种功能的前景。将NSC促分裂原Sonic hedgehog和Notch配体Delta移植到可溶性脂质体和合成表面上以调节细胞增殖和分化。该建议将探索这些合成的细胞效应物的结构-活性关系。将研究效应物效价、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。 我们的具体目标是：1。确定展示Sonic hedgehog或Delta的合成可溶性脂质体构建体是否可以控制NSC功能。 2.分析用Sonic hedgehog或Delta功能化的仿生表面是否可以有效地调节NSC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.