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

Nature Medicine volume 2, pages 1329–1337 (1996)Cite this article

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.

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Author information

Author notes

  1. Josef Vormoor

    Present address: Department of Paediatric Haematology/Oncology, University of Muenster, 48129, Muenster, Germany

  2. Thomas Moritz

    Present address: Department of Internal Medicine (Tumorklinik), University of Essen, 45122, Essen, Germany

  3. Tsvee Lapidot

    Present address: Department of Immunology, Weizmann Institute of Science, Rehovot, Israel, 76100

  4. André Larochelle and Josef Vormoor: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Genetics, Research Institute, Hospital for Sick Children,

    André Larochelle, Josef Vormoor, Jean C.Y. Wang, Mickie Bhatia, Tsvee Lapidot, Barbara Murdoch & John E. Dick

  2. Department of Molecular and Medical Genetics, University of Toronto, 555 University Avenue, Toronto, Ontario, Canada, M5G 1X8

    André Larochelle, Josef Vormoor, Jean C.Y. Wang, Mickie Bhatia, Tsvee Lapidot, Barbara Murdoch & John E. Dick

  3. Herman Wells Center for Pediatric Research, James Whitcomb Riley Hospital for Children, and Howard Hughes Medical Institute, Indiana University School of Medicine, Indianapolis, Indiana, 46202-5225, USA

    Helmut Hanenberg, Thomas Moritz, Xiang Li Xiao & David A. WIlliams

  4. Biotechnology Research Laboratories, Takara Shuzo Co. Ltd., Seta 3-4-1, Otsu, Shiga, 520-21, Japan

    Ikunoshin Kato

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Larochelle, A., Vormoor, J., Hanenberg, H. et al. Identification of primitive human hematopoietic cells capable of repopulating NOD/SCID mouse bone marrow: Implications for gene therapy. Nat Med 2, 1329–1337 (1996). https://doi.org/10.1038/nm1296-1329

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