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

该项目研究血管来源的干细胞自发组织成模式的机制，然后利用这些机制设计一些简单的模式形成控制。在我们之前使用发展中的干细胞培养系统的偏微分方程模型的工作的基础上，我们将开发一系列预测，解决改变边界条件如何改变模式的出现、大小、形状和其他参数。我们将通过在模型中加入细胞和细胞运动来扩展我们之前的建模工作，以前的模型是纯化学的。我们还将研究底物的机械和化学性质如何改变进化模式，以及细胞增殖和运动的特征如何影响模式。这一预测将在血管来源的成人干细胞的实验培养系统中得到验证。细胞自组织成结构模式(“模式形成”)的过程对许多生物过程是必不可少的。例如，胚胎的发育可以被视为这些过程的序列。为了能够成功地进行组织工程，了解这些过程的机制显然是很重要的。在过去，组织工程的一种常见方法是决定需要什么样的模式，然后尝试使用直接的外部控制来产生这种模式，而不理解潜在的生物组织原理。然而，生物系统的特点是其自组织能力，这可以击败和挫败模式控制的直接尝试。在这里，我们建议利用干细胞的自组织行为来推导出工程方法，以解决将复杂的生物系统诱骗成所需形式的反问题。我们认为，边界的形状、生长表面的弹性和化学性质以及细胞的迁移倾向是形成图案的重要因素。我们预计，从这项研究中获得的见解将对实现生物复杂结构的组织工程的尝试产生积极影响。

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.