首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Long-term in vivo monitoring of mouse and human hematopoietic stem cell engraftment with a human positron emission tomography reporter gene
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Long-term in vivo monitoring of mouse and human hematopoietic stem cell engraftment with a human positron emission tomography reporter gene

机译:人类正电子发射断层扫描报告基因对小鼠和人类造血干细胞移植的长期体内监测

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摘要

Positron emission tomography (PET) reporter genes allow nonin-vasive whole-body imaging of transplanted cells by detection with radiolabeled probes. We used a human deoxycytidine kinase containing three amino acid substitutions within the active site (hdCK3mut) as a reporter gene in combination with the PET probe [~(18)F]-L-FMAU (1-(2-deoxy-2-~(18)fluoro-β-L-arabinofuranosyl)-5-meth-yluracil) to monitor models of mouse and human hematopoietic stem cell (HSC) transplantation. These mutations in hdCK3mut expanded the substrate capacity allowing for reporter-specific detection with a thymidine analog probe. Measurements of long-term engrafted cells (up to 32 wk) demonstrated that hdCK3mut expression is maintained in vivo with no counter selection against reporter-labeled cells. Reporter cells retained equivalent engraftment and differentiation capacity being detected in all major hematopoietic lineages and tissues. This reporter gene and probe should be applicable to noninvasively monitor therapeutic cell transplants in multiple tissues.
机译:正电子发射断层扫描(PET)报告基因可以通过放射性标记的探针进行检测,从而对移植细胞进行无创全身成像。我们与PET探针[〜(18)F] -L-FMAU(1-(2-deoxy-2-〜)结合使用了在活性位点(hdCK3mut)中包含三个氨基酸取代的人脱氧胞苷激酶作为报告基因。 (18)fluoro-β-L-arabinofuranosyl)-5-meth-yluracil)来监测小鼠和人类造血干细胞(HSC)移植的模型。 hdCK3mut中的这些突变扩大了底物的容量,允许使用胸苷类似物探针进行报告基因特异性检测。长期移植细胞(长达32 wk)的测量结果表明,hdCK3mut表达在体内得以维持,而没有针对报道分子标记的细胞进行反选择。报告细胞保留了在所有主要造血谱系和组织中检测到的等效移植和分化能力。该报道基因和探针应适用于无创监测多种组织中的治疗性细胞移植。

著录项

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  • 作者单位

    Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095;

    Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, CA 90095;

    Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095;

    Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, CA 90095;

    Molecular Biology Institute, University of California, Los Angeles, CA 90095;

    Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095;

    Howard Hughes Medical Institute, University of California, Los Angeles, CA 90095;

    Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, CA 90095;

    Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, CA 90095,Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, CA 90095,Department of Pediatrics, University of California, Los Angeles, CA 90095;

    Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095,Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, CA 90095,Molecular Biology Institute, University of California, Los Angeles, CA 90095,Howard Hughes Medical Institute, University of California, Los Angeles, CA 90095,Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, CA 90095;

  • 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

    gene therapy; molecular imaging;

    机译:基因治疗;分子成像;

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