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In vivo Imaging of Growth Plate Dynamics

生长板动力学的体内成像

基本信息

批准号：
7590082
负责人：
CORNELIA ELLEN FARNUM
金额：
$ 16.33万
依托单位：
CORNELL UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-03-15 至 2010-02-28
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): Bone elongation in children occurs by endochondral ossification in cartilaginous growth plates at the ends of long bones. The parent R01 entitled In vivo Imaging of Growth Plate Dynamics funds a project using multiphoton microscopy to visualize molecular transport and cellular dynamics in growth plate cartilage of living mice. These studies have led to specific questions concerning oxygen levels within growth cartilage, and their relationship both to cellular metabolism during chondrogenic differentiation and to signaling cascades leading to vascular invasion of cartilage from metaphyseal endothelial cells. Although for more than fifty years experimental data have suggested that there is an O2 gradient within the growth plate extracellular matrix (ECM) that has an essential role in chondrocytic differentiation, definitive measurements still are inconclusive with conflicting results depending upon the methodology and the experimental system. What contributes to the ambiguity concerning O2 delivery to, and movement within, the growth plate cartilage ECM is that researchers are unable to directly map O2 concentrations within and around the region in vivo. Our BIRT proposal describes a highly interdisciplinary effort to produce oxygen-sensitive phosphors based on ruthenium complexes that are bright, sensitive and stable. Tailored for multiphoton microscopy, they will yield rapid micron-resolved images of O2 tension relatively deep into and around the growth cartilage of mice in vivo. Candidate sensors will be tested not only for their photophysical properties, but also for how they interact and function within tissue. Probe developments will be applicable both to confocal and multiphoton microscopy, and potentially whole animal "molecular imaging" systems. Our goal is to relate microenvironmental O2 levels to specific stages of chondrocytic differentiation, and to correlate O2 gradients within the ECM with O2 availability levels in three different surrounding vascular routes. The multidisciplinary team assembled for this BIRT award combines the expertise of a chemist with experience in designing oxygen-sensing probes, a nanotechnologist with skills in designing non-toxic delivery systems, a physicist with expertise in using multiphoton microscopy for radiometric measurements and in vivo imaging systems, and a biologist whose research has focused on cellular dynamics of the chondrocytic differentiation cascade in the postnatal animal.

描述(申请人提供)：儿童的骨延长是由长骨末端的软骨生长板中的软骨内骨化引起的。名为生长板动力学活体成像的母公司R01资助了一个使用多光子显微镜的项目，以可视化活着的小鼠生长板软骨中的分子运输和细胞动力学。这些研究导致了关于生长软骨内氧水平的具体问题，以及它们与软骨形成分化过程中的细胞代谢以及干骺端内皮细胞导致软骨血管侵袭的信号级联的关系。尽管50多年来的实验数据表明，生长板细胞外基质(ECM)中存在一个在软骨细胞分化中起重要作用的O2梯度，但最终的测量结果仍然没有定论，结果相互矛盾，这取决于方法和实验系统。造成氧向生长板软骨ECM输送和在生长板软骨ECM内运动的模棱两可的原因是，研究人员无法在活体内直接绘制该区域内和周围的O2浓度。我们的BIRT计划描述了一种高度跨学科的努力，以明亮、灵敏和稳定的Ru络合物为基础生产氧敏感荧光粉。为多光子显微镜量身定做的它们将产生快速微米分辨率的氧气张力图像，这些图像相对深入和环绕小鼠体内生长的软骨。候选传感器不仅要测试它们的光物理特性，还要测试它们在组织内如何相互作用和发挥作用。探针的发展将同时适用于共焦显微镜和多光子显微镜，并可能适用于整个动物的“分子成像”系统。我们的目标是将微环境中的O2水平与软骨细胞分化的特定阶段联系起来，并将ECM内的O2梯度与周围三条不同血管途径中的O2可获得性水平联系起来。为BIRT奖组建的多学科团队结合了以下几个方面的专业知识：一位在设计氧气传感探头方面有经验的化学家，一位在设计无毒输送系统方面有技能的纳米技术专家，一位在使用多光子显微镜进行辐射测量和活体成像系统方面的专业知识，以及一位生物学家，他的研究重点是出生后动物软骨细胞分化级联的细胞动力学。