Tissue Engineered Cartilage Repair: Molecular Imaging of Condrogenesis

描述（由申请人提供）：具有骨或软骨特异性启动子的三重融合报告基因系统将用于基于细胞的组织工程化构建体中，以对植入细胞的合成活性（分化和增殖）进行非侵入性和实时成像，以优化软骨修复/再生。我们目前有一个NIAMS资助的P01，题为“组织工程软骨修复”（P01），这是使用最先进的组织工程来解决关节软骨修复的问题。NIAMS提供这个BIRT机会，以补充现有的奖项，如我们的P01，并考虑支持建立新的跨学科合作的具体领域之一是“软组织生物学-成像技术”。在过去的几年里，我们在干细胞移植和植入的分子成像方面取得了很大的进步。我们现在很好地定位于提出新的和特定的成像技术，其通过实现与基于干细胞和/或软骨细胞的软骨修复和再生相关的分子事件的非侵入性、实时和定量监测来增加P01的价值，所述分子事件例如标记基因Col I、Col II、Col X等的表达，加强所有现有的项目以及现有核心项目中的研究部分。目前，P01中的所有实验读数或终点分析均基于免疫组织化学、定量组织形态学和生物力学测试。虽然所有这些都被认为是结果测量的“黄金标准”，但是非常需要并且目前无法获得用于跟踪软骨修复期间的关键事件的非破坏性（用于体外实验）和非侵入性（用于体内动物研究）、纵向和定量手段。我们的长期目标是创建一个将集成到现有P01中的分子成像核心。该BIRT项目将给母基金（P01）带来的主要影响是将体内/离体实验与体内动物研究联系起来。本文提出的分子成像技术将提供以前从未见过的分子和细胞水平的数据，这不仅有助于研究基于干细胞的软骨修复，而且还增加了我们对软组织生物学的了解。

DESCRIPTION (provided by applicant): A triple fusion reporter gene system with bone or cartilage specific promoters will be used in cell-based tissue engineered constructs to perform non-invasive and real-time imaging of synthetic activities (differentiation & proliferation) of implanted cells for optimizing cartilage repair/regeneration. We currently have a NIAMS-funded P01 entitled "Tissue Engineered Cartilage Repair" (P01), which is to use state-of-the-art tissue engineering to address issues of articular cartilage repair. NIAMS is offering this BIRT opportunity to supplement existing awards such as our P01, and one of the specific areas to be considered for support to establish new interdisciplinary collaboration is "Soft Tissue Biology - Imaging Technologies". During past few years, we have made great strides in molecular imaging of stem cell transplants and implants. We are now well positioned to propose novel and specific imaging techniques that add value to the P01 by enabling non-invasive, real-time and quantitative monitoring of molecular events associated with stem cell and/or chondrocyte based cartilage repair and regeneration such as the expression of marker genes Col I, Col II, Col X, etc., to enhance all existing Projects as well as the research components within the existing Cores. Currently, all experimental read-outs or end-point analyses in the P01 are based on immuno-histochemistry, quantitative histomorphometry, and biomechanical tests. While all these are considered the "gold standards" for outcome measures, a non-destructive (for in vitro experiments) and non-invasive (for in vivo animal studies), longitudinal, and quantitative means for tracking key events during cartilage repair down to the molecular level is much needed and currently unavailable. Our long-term goal is to create a Molecular Imaging Core that will be integrated into the existing P01. The major impact that this BIRT project will bring into the parent grant (P01) is to connect in vivo/ex vivo experiments with in vivo animal studies. Molecular imaging techniques proposed here will provide the kind of data at molecular and cellular level not seen before, which will not only aid the investigation of stem cell-based cartilage repair, but also add to our knowledge of soft tissue biology.