BECS: Pattern Formation by Vascular Stem Cells: Control of Complex Biological Systems through Bottom-up and Top-down Approaches

BECS：血管干细胞的模式形成：通过自下而上和自上而下的方法控制复杂的生物系统

• 批准号: 1025073
• 负责人: Alan Garfinkel
• 金额: $ 31万
• 依托单位: University of California-Los Angeles
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-01 至 2012-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1025073&HistoricalAwards=false
• 关键词: BECS; Pattern; Formation; Vascular; Stem; BECS; Pattern; Formation; Vascular; Stem

This project studies the mechanisms by which vascular-derived stem cells spontaneously organize into patterns, and then uses these mechanisms to devise some simple controls on pattern formation. Building on our previous work using Partial Differential Equation models of the developing stem cell culture system, we will develop a series of predictions addressing how altered boundary conditions change the occurrence, size, shape and other parameters of the pattern. We will extend our previous modeling efforts by incorporating cells and cell movement in the model, which had previously been purely chemical. We will also study how the mechanical and chemical properties of the substrate alter the evolving pattern, and how the features of cell proliferation and movement affect the pattern. Predictions will be tested in an experimental culture system of vascular-derived adult stem cells. The process by which cells self-organize into structured patterns ("pattern formation") is essential to many biological processes. The development of the embryo, for example, can be viewed as a sequence of these processes. It is clearly important to understand the mechanisms of these processes in order to be able to do successful ?tissue engineering?. In the past, a common approach to tissue engineering has been to decide what patterns are desired, and then to attempt to use direct external controls to produce that pattern, without an understanding of the underlying biological organizational principles. However, biological systems are characterized by their capacity for self-organization, which can defeat and frustrate direct attempts at pattern control. Here, we propose to take advantage of the self-organizational behavior of stem cells to derive engineering approaches to the inverse problem of coaxing complex biological systems into a desired form. We believe that the shape of the boundary, the elastic and chemical properties of the surface on which they are grown, and the migratory tendencies of the cells are important contributors to pattern formation. We expect that insights gained from this study will have a positive impact on attempts to achieve tissue engineering of biological complex structures.

该项目研究了血管衍生的干细胞自发组织成模式的机制，然后使用这些机制来设计一些简单的控制模式形成。在我们先前使用开发干细胞培养系统的部分微分方程模型的工作的基础上，我们将开发一系列预测，以解决边界条件如何改变模式的发生，大小，形状和其他参数。我们将通过在模型中纳入细胞和细胞运动来扩展以前的建模工作，该模型以前纯化学。我们还将研究底物的机械和化学特性如何改变不断发展的模式，以及细胞增殖和运动的特征如何影响模式。预测将在血管来源的成年干细胞的实验培养系统中进行测试。细胞自组织成结构化模式（“模式形成”）的过程对于许多生物过程至关重要。例如，可以将胚胎的开发视为这些过程的序列。理解这些过程的机制以便能够成功吗？组织工程显然很重要吗？过去，组织工程的一种常见方法是决定需要哪些模式，然后尝试使用直接的外部控制来产生该模式，而不必了解基本的生物组织原理。 但是，生物系统的特征是它们的自我组织能力，这可能会失败并挫败直接尝试模式控制的尝试。 在这里，我们建议利用干细胞的自组织行为，从而导致工程方法将复杂的生物系统诱使所需形式的反向问题。我们认为，边界的形状，它们生长的表面的弹性和化学特性以及细胞的迁移趋势是模式形成的重要促进者。我们希望从这项研究中获得的见解将对实现生物复合结构组织工程的尝试产生积极影响。