Bioengineering Approach for Advancing Reparative Medicine Stem Cell Technologies

推进修复医学干细胞技术的生物工程方法

基本信息

批准号：
10673032
负责人：
WALTER L MURFEE
金额：
$ 18.18万
依托单位：
UNIVERSITY OF FLORIDA
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-08-01 至 2024-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10673032
关键词：
Adipose tissue Adult Attention Basic Science Biological Models Biomedical Engineering Biomimetics Bioreactors Blood Blood Vessels CSPG4 gene Cell Fraction Cells Clinical Development DsRed Endothelial Cells Environment Evaluation Generations Goals Growth Heart Research Intercellular Junctions Investigation Knock-out Knowledge Laboratories LoxP-flanked allele Lung Lymphangiogenesis Lymphatic Modeling Mus Myocardial Ischemia National Heart, Lung, and Blood Institute Perfusion Pericytes Permeability Physiological Population Positioning Attribute Rattus Research Sleep Disorders System Technology Therapeutic Uses Time Tissues Transgenic Mice Transplantation Work angiogenesis clinical translation density design ex vivo perfusion innovation interest malformation model development molecular dynamics neovascularization neovasculature network models new technology novel novel therapeutics pre-clinical reparative medicine stem cell technology technology development tissue culture tissue repair tool

项目摘要

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.

项目摘要该提案的目的是开发一种模型技术，以实现脂肪的临床前研究在真正的灌注微血管网络环境中，衍生的基质血管分数（SVF）几天的过程。这样的模型不存在。 SVF移植是一种有希望的新疗法基于SVF可以形成新容器的想法，从心脏缺血到组织修复的应用。较大的知识差距仍然与从头血管生长的时间过程有关（即新血管化）， SVF派生的血管与附近的微血管网络的整合，以及新的细胞构成船只。了解SVF细胞在何处以及如何促进微血管生长将有助于指导其治疗用途。 PI的实验室已经开发并验证了新老鼠的身体相关性组织培养模型，可以实时对完整成人微血管中细胞动力学的实时观察网络。这种仿生的“视图”导致发现与内皮细胞动力学和淋巴/血管可塑性。 PI的实验室还开发了一种生物反应器来引入灌注在培养的微血管网络中，现在是将这些方法与鼠组织开发一种全新的技术，用于评估SVF命运和功能（图1）。 SVF 疗法尚未发挥潜力。我们的新型高含量工具将启用多细胞/系统血管生成，淋巴管生成和血管渗透性的读数将定义SVF的范围符合NHLBI特别关注通知的目的，目的是发展和发现的目标是产生新的假设。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以建立一种灌注的微血管网络模型来评估SVF 新血管形成。目标2：对假设生成项目的影响 - 确定神经胶质抗原的影响2 （NG2）抑制SVF新血管化。拟议的研究将为发现SVF动态和效果的新“视图” 在生理上相关的微血管环境与其他模型不可能进行读数。长期这项工作的目的是了解和评估潜在的SVF疗法。该提议将证明基础科学研究的仿生平台的价值专注于识别SVF动力学和阐明环境，细胞和特定分子动力学如何指导SVF治疗。

项目成果

期刊论文数量（4）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Estimation of shear stress heterogeneity along capillary segments in angiogenic rat mesenteric microvascular networks.

估计血管生成大鼠肠系膜微血管网络中沿毛细血管段的剪切应力异质性。

DOI：
10.1111/micc.12830
发表时间：
2023
期刊：
Microcirculation (New York, N.Y. : 1994)
影响因子：
0
作者：
Hu,Nien-Wen;Lomel,BanksM;Rice,ElijahW;Hossain,MirMdNasim;Sarntinoranont,Malisa;Secomb,TimothyW;Murfee,WalterL;Balogh,Peter
通讯作者：
Balogh,Peter

Angiogenic Microvascular Wall Shear Stress Patterns Revealed Through Three-dimensional Red Blood Cell Resolved Modeling.