Tracking cardiac engraftment and viability of MiPSC by MRI

 描述(由申请人提供)：项目摘要/摘要为了利用细胞疗法的潜力，需要对细胞移植后的细胞有更多的了解。我们的目标是通过实验验证磁内共生生物(MES)作为一种活的MRI造影剂，通过在体内展示活细胞特异性(LCS)来深入了解干细胞在心脏和神经损伤模型中的植入和生存能力。生物发光和商业核磁共振造影剂将被用作验证和展示竞争优势的对照。记者基因方法有LC，但也有其他并发症，例如需要基因工程，这会使监管发展复杂化。现有的MRI造影剂提供了完整的解剖通道，但由于巨噬细胞摄取和非特异性信号，缺乏LCS。我们的初步结果表明，MES可以在不干扰细胞功能的情况下，成功地标记心肌细胞(ICM)和人类神经前体细胞(HNPC)。ME标记的ICM在体内成功植入并可视化2周(第一阶段的总目标)。此外，初步结果表明MES提供LCS，而被动MRI试剂不提供LCS。在第二阶段，我们建议在这一积极进展的基础上，在第二个模型(HNPC)中充分展示基于ME的细胞跟踪的价值，并在实验上坚定地定义两个模型中的LCS竞争优势。能够以最小的毒性有效和特异地标记体内细胞的成像试剂的开发解决了细胞治疗的关键障碍。这样的工具将通过提供优化细胞疗法所需的生物分布和生存能力的信息，降低研发和临床试验的资本投资风险。

 DESCRIPTION (provided by applicant): Project Summary/Abstract In order to harness the potential of cell therapies, more needs to be understood about cells post transplantation. Our goal is to experimentally validate magnetoendosymbionts (MEs) as a living MRI contrast agent to provide this insight into stem cell engraftment and viability in cardiac and neural injury model by demonstrating live cell specificity (LCS), in vivo. Bioluminescence and commercial MRI contrast agents will be used as controls for validation and to demonstrate competitive advantages. Reporter gene approaches have LCS but suffer from other complications such as need for genetic engineering that complicates regulatory developments. Existing MRI contrast agents provide full anatomic access, but lack LCS due to uptake by macrophages and nonspecific signal. Our preliminary results suggest that MEs can be used to successfully label cardiomyoctyes (iCMs) and human neural progenitor cells (hNPCs), without perturbing cell function. ME- labeled iCMs were successfully engrafted and visualized for 2 weeks in vivo (the overall goal of Phase 1). Moreover, preliminary results suggest MEs provide LCS whereas the passive MRI agent did not. In Phase 2, we propose to extend from this positive progress and fully demonstrate the value of ME- based cell tracking in a second model (hNPCs) and firmly experimentally define the LCS competitive advantage in both models. Development of imaging reagents that can effectively and specifically label cells in vivo with minimal toxicity addresses critical barrier for the cell therapies. Such a tool will lower the risk of capital investments forR&D and clinical trials, by providing the information on bio-distribution and viability needed to optimize cell therapies.