Analysis of the Developmental Potential of USSC in vitro and in vivo

USSC体内外发育潜力分析

• 批准号: 55927872
• 负责人: Professor Dr. Jürgen Schrader
• 金额: --
• 依托单位: Institut für Molekulare Kardiologie
• 依托单位国家: 德国
• 项目类别: Research Units
• 财政年份: 2007
• 资助国家: 德国
• 起止时间: 2006-12-31 至 2010-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/55927872?language=en
• 关键词: Analysis; Developmental; Potential; USSC; vitro

Cardiomyogenic differentiation of USSCs was successfully demonstrated in co-culture, and invivo, USSCs transplanted into the infracted rat heart was shown to improve cardiac function despite significant loss of transplanted cells over time. We now aim to define the cellular and molecular mechanism(s) underlying USSC-mediated cardiac repair and to improve the quality of transplanted USSC by taking the following steps. Firstly, heart interstitial fluid (obtained in “reversed heart” model) will be subject to differential proteomic (DIGE) and cytokine/chemokine (Bioplex) analysis to define potential bio-effective paracrine factors released from USSC-treated hearts. Secondly, the role of inflammatory (CD45+, CD11b+, CD3+) and resident cardiac stem cells (c-kit+, ist1+) will be quantitatively assessed in center, border and remote zone of the infarct heart by FACS analysis as well as by using of 19F-MRI in vivo. Thirdly, cardiac committed cell will be generated by genetic overexpression of SOX17, TBX5 and MEF2c in USSCs and the functional relevance will be investigated in co-culture and in-vivo experiments to determine whether this will enhance the survival and integration of USSCs after transplantation.

USSCs 的心肌分化在共培养中得到成功证明，并且在体内，尽管随着时间的推移移植细胞明显损失，但移植到梗塞大鼠心脏中的 USSCs 仍能改善心脏功能。我们现在的目标是确定 USSC 介导的心脏修复的细胞和分子机制，并通过采取以下步骤来提高移植 USSC 的质量。首先，心脏间质液（在“逆转心脏”模型中获得）将进行差异蛋白质组学 (DIGE) 和细胞因子/趋化因子 (Bioplex) 分析，以确定 USSC 处理的心脏释放的潜在生物有效旁分泌因子。其次，通过 FACS 分析以及体内 19F-MRI 定量评估梗塞心脏中心、边缘和远端区域炎症（CD45+、CD11b+、CD3+）和驻留心脏干细胞（c-kit+、ist1+）的作用。第三，心脏定型细胞将通过USSC中SOX17、TBX5和MEF2c的基因过表达来产生，并且将在共培养和体内实验中研究其功能相关性，以确定这是否会增强移植后USSC的存活和整合。