Bioengineering Approach for Advancing Reparative Medicine Stem Cell Technologies

项目摘要 这项提议的目标是开发一种模型技术，使脂肪的临床前研究成为可能 真实灌流微血管网络环境中衍生间质血管分数(SVF)随时间的变化 当然是几天了。这样的模式并不存在。SVF移植是一种很有前途的新疗法 基于SVF可以形成新血管的理念，从心肌缺血到组织修复的各种应用。 关于新生血管生长的时间进程(即新生血管)，仍然存在巨大的知识差距， SVF来源的血管与邻近的微血管网络的整合以及新的细胞组成 船只。了解SVF细胞在哪里以及如何促进微血管生长将有助于指导他们的 治疗用途。PI的实验室已经开发并验证了一种新的大鼠的生理相关性 能够实时体外观察完整成人微血管细胞动力学的组织培养模型 网络。这种仿生的“观点”导致了与内皮细胞动力学和 淋巴管/血管可塑性。PI的实验室还开发了一种生物反应器，用于引入灌流 在培养的微血管网络中，现在具有独特的地位，可以将这些方法与 为评估SVF的命运和功能开发一种全新的技术(图1)。SVF 治疗方法尚未发挥其潜力。我们的新型高内容工具将支持多单元/系统 定义SVF范围的血管生成、淋巴管生成和血管通透性的读数 冲击力。与特别关注的NHLBI通知的目的一致，目的是发展和 以产生新假说为目标的发现驱动。 目标1：发现SVF命运和功能的模型开发-将生物反应器设计与 组织培养建立评价SVF的灌流微血管网络模型 新生血管。 目标2：对假说生成项目的影响--确定神经胶质抗原2的影响 (NG2)抑制SVF新生血管形成。 提出的研究将为发现SVF的动力学和效应提供一个新的视角。 生理上相关的微血管环境，读数在其他模型中是不可能的。长期的 这项工作的目的是了解和评估潜在的SVF治疗方法。这项提议将证明 用于基础科学研究的仿生平台的价值侧重于识别SVF动力学和阐明 环境、细胞和特定的分子动力学如何指导SVF治疗。

Project Summary The goal of this proposal is to develop a model technology that enables pre-clinical investigation of adipose derived stromal vascular fraction (SVF) in a real perfused microvascular network environment over the time course of a few days. Such a model does not exist. SVF transplantation is a promising new therapy for applications spanning from cardiac ischemia to tissue repair based on the idea that SVF can form new vessels. Big knowledge gaps remain relating to the time course of the de novo vessel growth (i.e. neovascularization), the integration of SVF derived vessels with nearby microvascular networks, and the cell makeup of the new vessels. Understanding where and how SVF cells contribute to microvascular growth will help guide their therapeutic use. The PI's laboratory has developed and validated the physiological relevance of a novel rat tissue culture model that enables real-time ex vivo observation of cell dynamics in intact adult microvascular networks. This biomimetic “view” has led to discoveries related to endothelial cell dynamics and lymphatic/blood vessel plasticity. The PI's laboratory has also developed a bioreactor for introducing perfusion in the cultured microvascular networks and is now uniquely positioned to combine these approaches with murine tissue to develop a totally new technology for evaluating SVF fate and function (Figure 1). SVF therapies have not yet reached their potential. Our novel high-content tool will enable multi-cell/system readouts for angiogenesis, lymphangiogenesis, and vessel permeability that will define the scope of SVF impact. In line with the purpose of the NHLBI notice of special interest, the aims are development and discovery driven with the goal of generating new hypotheses. Aim 1: Model Development for Discovery of SVF Fate and Function – To combine bioreactor design with tissue culture to establish a perfused microvascular network model for evaluating SVF neovascularization. Aim 2: Impact for Hypothesis Generation Projects – To determine the impact of neuron-glial antigen 2 (NG2) inhibition on SVF neovascularization. The proposed research will offer a new “view” for the discovery of SVF dynamics and effects in a physiologically relevant microvascular milieu with readouts not possible with other models. The long-term objective of this work is to understand and evaluate potential SVF therapies. This proposal will demonstrate the value of a biomimetic platform for basic science studies focused on identifying SVF dynamics and elucidating how environmental, cellular, and specific molecular dynamics might guide SVF therapy.