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: 8319267
• 负责人: JEREMY J MAO
• 金额: $ 54.78万
• 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 2014-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8319267
• 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）： 作为对PAR-06-504“组织工程和再生医学的使能技术”的回应，我们提出了一种通过非破坏性和非侵入性成像在体内和真实的时间用生物缀合的量子点（QD）跟踪干细胞的使能技术。与发育生物学类似，组织再生中的一个常见挑战是追踪真实的发育中的细胞和组织。我们的初步数据表明，生物缀合的量子点是安全的，以标记人骨髓间充质干细胞（hMSCs）在增殖的几个通道，以及分化成软骨细胞和成骨细胞。我们还表明，量子点标记的hMSCs，通过尾静脉注射的SCID小鼠，可以在体内和实时跟踪的全身成像系统。此外，我们能够在体内和真实的实时追踪皮下注射的多重QD标记的hMSC。这些发现导致了我们的总体假设，即干细胞系统地运送到局部缺损并参与缺损愈合，这在以前由于缺乏体内和真实的时间细胞跟踪模式而难以研究。该提案的总体目标是确定QD标记和追踪MSC在体内和真实的时间的功效，并提高我们对不同细胞群体对组织缺损愈合的相对贡献的理解。我们的长期目标是将QD标记用于细胞追踪，作为用于其他组织（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-肌腱连接处等）愈合的平台技术。 公共卫生相关性声明（由申请方提供）：该项目有可能证明标记干细胞并在体内和真实的时间内跟踪再生组织发育的可行方法。它也有可能有助于我们理解工程骨软骨界面，这在关节炎关节的生物工程置换中具有关键价值。

项目成果

Regenerative endodontics: barriers and strategies for clinical translation.

• DOI: 10.1016/j.cden.2012.05.005
• 发表时间: 2012-07
• 期刊: Dental clinics of North America
• 作者: Mao JJ;Kim SG;Zhou J;Ye L;Cho S;Suzuki T;Fu SY;Yang R;Zhou X
• 通讯作者: Zhou X

Musculoskeletal tissue engineering by endogenous stem/progenitor cells.

内源干/祖细胞的肌肉骨骼组织工程。

• DOI: 10.1007/s00441-012-1339-2
• 发表时间: 2012
• 期刊: Cell and tissue research
• 影响因子: 3.6
• 作者: Nie,Hemin;Lee,ChangHun;Tan,Jiali;Lu,Chuanyong;Mendelson,Avital;Chen,Mo;Embree,MildredC;Kong,Kimi;Shah,Bhranti;Wang,Shuang;Cho,Shoko;Mao,JeremyJ
• 通讯作者: Mao,JeremyJ