Transfer of marker genes into hemopoietic progenitor cells.

Cytokines and molecular therapy Pub Date : 1996-09-01
M K Brenner, H E Heslop, D Rill, C Li, C Smith, R Krance, C Rooney
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Abstract

Ex vivo gene marking of normal and malignant hemopoietic cells allows the cells to be subsequently tracked in vivo. Marking has shown that even when marrow is in remission, it may contain malignant cells that contribute to relapse. These studies have also shown that it is possible to obtain long-term gene expression in human long-lived hemopoietic progenitor cells and T lymphocytes in vivo. Current marker studies use two distinguishable vectors to track two distinctively treated cell populations in a single individual. This modification greatly increases the power of the technique. It is now possible to study the effects of purging on residual malignant cells in marrow, to determine the action of growth-promoting agents (such as cytokines and stroma) on short- and long-term repopulation by transduced marrow, and to discover which phenotypic subsets of hemopoietic progenitor cells have long-term repopulating potential. The information gained will be invaluable for improving therapeutic gene transfer protocols in which marrow-derived cells are the targets.

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标记基因转移到造血祖细胞。
正常和恶性造血细胞的离体基因标记允许细胞随后在体内被跟踪。标记表明,即使骨髓处于缓解期,它也可能含有导致复发的恶性细胞。这些研究也表明,在人体内长寿造血祖细胞和T淋巴细胞中获得长期基因表达是可能的。目前的标记研究使用两种可区分的载体来跟踪单个个体中两个不同处理的细胞群。这种修改大大增加了技术的威力。现在有可能研究清除对骨髓中残留恶性细胞的影响,确定生长促进剂(如细胞因子和基质)对转导骨髓短期和长期再生的作用,并发现造血祖细胞的哪些表型亚群具有长期再生潜力。所获得的信息将是无价的,以改善治疗基因转移方案,其中骨髓来源的细胞是目标。
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