Identification of primitive human hematopoietic cells capable of repopulating NOD/SCID mouse bone marrow: Implications for gene therapy

André Larochelle, Josef Vormoor, Helmut Hanenberg, Jean C.Y. Wang, Mickie Bhatia, Tsvee Lapidot, Thomas Moritz, Barbara Murdoch, Xiang Li Xiao, Ikunoshin Kato, David A. Williams, John E. Dick

Research output: Contribution to journalArticle

615 Scopus citations

Abstract

The development of stem-cell gene therapy is hindered by the absence of repopulation assays for primitive human hematopoietic cells. Current methods of gene transfer rely on in vitro colony-forming cell (CFC) and long-term culture-initiating cell (LTC-IC) assays, as well as inference from other mammalian species. We have identified a novel human hematopoietic cell, the SCID-repopulating cell (SRC), a cell more primitive than most LTC-ICs and CFCs. The SRC, exclusively present in the CD4+CD8- fraction, is capable of multilineage repopulation of the bone marrow of nonobese diabetic mice with severe combined immunodeficiency disease (NOD/SCID mice). SRCs were rarely transduced with retroviruses, distinguishing them from most CFCs and LTC-ICs. This observation is consistent with the low level of gene marking seen in human gene therapy trials. An SRC assay may aid in the characterization of hematopoiesis, as well as the improvement of transduction methods.

Original languageEnglish (US)
Pages (from-to)1329-1337
Number of pages9
JournalNature Medicine
Volume2
Issue number12
DOIs
StatePublished - Dec 1 1996

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Larochelle, A., Vormoor, J., Hanenberg, H., Wang, J. C. Y., Bhatia, M., Lapidot, T., Moritz, T., Murdoch, B., Xiao, X. L., Kato, I., Williams, D. A., & Dick, J. E. (1996). Identification of primitive human hematopoietic cells capable of repopulating NOD/SCID mouse bone marrow: Implications for gene therapy. Nature Medicine, 2(12), 1329-1337. https://doi.org/10.1038/nm1296-1329