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Implantable microenvironments to attract hematopoietic stem/cancer cells

机译:可植入的微环境吸引造血干/癌细胞

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摘要

The environments that harbor hematopoietic stem and progenitor cells are critical to explore for a better understanding of hemato-poiesis during health and disease. These compartments often are inaccessible for controlled and rapid experimentation, thus limiting studies to the evaluation of conventional cell culture and trans-genic animal models. Here we describe the manufacture and image-guided monitoring of an engineered microenvironment with user-defined properties that recruits hematopoietic progenitors into the implant. Using intravital imaging and fluorescence molecular tomography, we show in real time that the cell homing and retention process is efficient and durable for short- and long-term engraftment studies. Our results indicate that bone marrow stromal cells, precoated on the implant, accelerate the formation of new sinusoidal blood vessels with vascular integrity at the micro-capillary level that enhances the recruitment hematopoietic progenitor cells to the site. This implantable construct can serve as a tool enabling the study of hematopoiesis.
机译:拥有造血干细胞和祖细胞的环境对于更好地了解健康和疾病期间的造血能力至关重要。这些隔室通常无法进行受控和快速实验,因此将研究限于常规细胞培养和转基因动物模型的评估。在这里,我们描述了具有用户定义属性的工程微环境的制造和图像引导监视,该环境可将造血祖细胞招募到植入物中。使用活体成像和荧光分子层析成像,我们实时显示了细胞归巢和保留过程对于短期和长期植入研究是有效且持久的。我们的结果表明,预涂在植入物上的骨髓基质细胞在微毛细血管水平上加速了具有血管完整性的新正弦血管的形成,从而增强了造血祖细胞的募集。这种可植入的构建体可以用作研究造血功能的工具。

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  • 作者单位

    Center for Engineering in Medicine and Surgical Services, Massachusetts General Hospital, Harvard Medical School and Shriners Hospital for Children in Boston, MA 02114;

    Center for Engineering in Medicine and Surgical Services, Massachusetts General Hospital, Harvard Medical School and Shriners Hospital for Children in Boston, MA 02114,Harvard-MIT Health Sciences and Technology, Cambridge, MA 02139;

    Center for Engineering in Medicine and Surgical Services, Massachusetts General Hospital, Harvard Medical School and Shriners Hospital for Children in Boston, MA 02114,Harvard-MIT Health Sciences and Technology, Cambridge, MA 02139;

    Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114;

    Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114;

    Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114;

    Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114;

    Center for Engineering in Medicine and Surgical Services, Massachusetts General Hospital, Harvard Medical School and Shriners Hospital for Children in Boston, MA 02114;

    Center for Engineering in Medicine and Surgical Services, Massachusetts General Hospital, Harvard Medical School and Shriners Hospital for Children in Boston, MA 02114;

    Section of Hematology, Department of Medicine, Haukeland University Hospital, 5021 Bergen, Norway;

    Gade Institute, University of Bergen, 5020 Bergen, Norway;

    Department of Hematology, Institute of Internal Medicine, Haukeland University Hospital, University of Bergen, 5020 Bergen, Norway;

    Department of Hematology, Institute of Internal Medicine, Haukeland University Hospital, University of Bergen, 5020 Bergen, Norway;

    Department of Hematology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02114,The Harvard Stem Cell Institute, Boston, MA 02115;

    Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114;

    Center for Engineering in Medicine and Surgical Services, Massachusetts General Hospital, Harvard Medical School and Shriners Hospital for Children in Boston, MA 02114,Department of Biomedical Engineering, Rutgers University, Piscataway, NJ 08854;

    Center for Engineering in Medicine and Surgical Services, Massachusetts General Hospital, Harvard Medical School and Shriners Hospital for Children in Boston, MA 02114,The Harvard Stem Cell Institute, Boston, MA 02115;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    hydrogel scaffolds; leukemia; mesenchymal stem cells; stem cell niche; tissue engineered bone marrow;

    机译:水凝胶支架白血病;间充质干细胞干细胞生态位组织工程骨髓;

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