Tracking stem cells in engineered tissue and organs in vivo and in real time

体内实时追踪工程组织和器官中的干细胞

• 批准号: 7691514
• 负责人: JEREMY J MAO
• 金额: $ 55.38万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-15 至 2013-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7691514
• 关键词: Adherent Culture; Adipocytes; Apoptosis; Arthritis; Back; Behavior; Biocompatible Materials; Biological Assay; Biomedical Engineering; Cardiac; Cell Proliferation; Cell Survival; Cell Transplants; Cells; Chondrocytes; Data; Defect; Development; Developmental Biology; Dyes; Encapsulated; Engineering; Goals; Healed; Home environment; Human; Human Activities; Hydrogels; Image; Implant; In Vitro; Joints; Label; Lead; Ligaments; Mechanics; Mesenchymal Stem Cells; Metabolism; Methods; Microscopic; Modality; Molecular; Mus; Muscle; Musculoskeletal; Natural regeneration; Neurons; Nude Rats; Organ; Osteoblasts; Outcome Assessment; Pancreas; Photobleaching; Population; Proliferating; Proteins; Quantum Dots; Rattus; Regenerative Medicine; Relative (related person); SCID Mice; Signal Transduction; Stem cells; System; Tail; Technology; Tendon structure; Testing; Time; Tissue Engineering; Tissues; Veins; Wound Healing; bone; cytotoxicity; healing; improved; in vivo; osteochondral tissue; public health relevance; response; scaffold; tissue regeneration; tool

DESCRIPTION (provided by applicant): In response to PAR-06-504 "Enabling Technologies for Tissue Engineering and Regenerative Medicine," we present an enabling technology of tracking stem cells with bioconjugated quantum dots (QDs) by non-destructive and non- invasive imaging, both in vivo and in real time. A common challenge in tissue regeneration, similar to developmental biology, is the tracking of cells and tissues that are developing in real time. Our preliminary data demonstrate that bioconjugated QDs are safe to label human mesenchymal stem cells (hMSCs) during proliferation for several passages, as well as differentiation into chondrocytes and osteoblasts. We also show that QD-labeled hMSCs, injected via the tail vein of SCID mice, can be tracked in vivo and in real-time by a whole body imager system. Furthermore, we were able to track multiplexing QD- labeled hMSCs injected subcutaneously in vivo and in real time. Theses findings lead to our overall hypothesis that stem cells delivered systemically home to local defects and participate in defect healing, which has been difficult to study previously due to the lack of in vivo and real time cell tracking modalities. The overall goal of this proposal is to determine the efficacy of QD labeling and tracking of MSCs in vivo and in real time, and to improve our understanding of the relative contribution of different cell populations to the healing of tissue defect. Our long-term goal is to apply QD labeling for cell tracking as a platform technology for the healing of other tissues such as cardiac, neuronal, and pancreatic, as well as other musculoskeletal tissues such as bone-ligament interface, muscle-tendon junction, etc. Public Health Relevance Statement (provided by applicant): This project has the potential to demonstrate a viable method for labeling stem cells and tracking the development of regenerating tissue in vivo and in real time. It also has a potential to contribute to our understanding of the engineered osteochondral interface that is of critical value in bioengineered replacement of arthritic joints.

描述（由申请人提供）： 为了响应 PAR-06-504“组织工程和再生医学的使能技术”，我们提出了一种利用生物共轭量子点（QD）通过体内和体内非破坏性和非侵入性成像跟踪干细胞的使能技术。即时的。与发育生物学类似，组织再生的一个常见挑战是实时跟踪正在发育的细胞和组织。我们的初步数据表明，生物共轭量子点在增殖数代以及分化为软骨细胞和成骨细胞期间可以安全地标记人间充质干细胞（hMSC）。我们还表明，通过 SCID 小鼠尾静脉注射的 QD 标记 hMSC 可以通过全身成像系统在体内实时跟踪。此外，我们能够实时跟踪体内皮下注射的多重 QD 标记 hMSC。这些发现引出了我们的总体假设，即干细胞系统地输送到局部缺陷并参与缺陷愈合，由于缺乏体内和实时细胞追踪方式，以前很难研究这一点。该提案的总体目标是确定 QD 标记和体内实时追踪 MSC 的功效，并提高我们对不同细胞群对组织缺损愈合的相对贡献的理解。我们的长期目标是应用用于细胞追踪的QD标记作为平台技术来治愈其他组织，如心脏、神经元和胰腺，以及其他肌肉骨骼组织，如骨韧带界面、肌肉肌腱连接处、 ETC。 公共卫生相关性声明（由申请人提供）：该项目有潜力展示一种标记干细胞并实时跟踪体内再生组织发育的可行方法。它还有可能有助于我们了解工程骨软骨界面，这对于关节炎关节的生物工程替代具有重要价值。