Identification of Primitive Human Hematopoietic Cells Capable of Repopulating NOD/SCID Mouse Bone Marrow: Implications for Gene Therapy

Nat Med. 1996 Dec;2(12):1329-37. doi: 10.1038/nm1296-1329.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • ADP-ribosyl Cyclase
  • ADP-ribosyl Cyclase 1
  • Animals
  • Antigens, CD*
  • Antigens, CD34 / analysis
  • Antigens, Differentiation / analysis
  • Bone Marrow Cells*
  • Cell Separation
  • Cells, Cultured
  • Coculture Techniques
  • Colony-Forming Units Assay / methods*
  • Fetal Blood / cytology
  • Fibroblasts
  • Fibronectins
  • Flow Cytometry
  • Gene Transfer Techniques*
  • Genetic Therapy
  • Hematopoietic Stem Cell Transplantation*
  • Hematopoietic Stem Cells*
  • Humans
  • Membrane Glycoproteins
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • N-Glycosyl Hydrolases / analysis
  • Peptide Fragments
  • Retroviridae


  • Antigens, CD
  • Antigens, CD34
  • Antigens, Differentiation
  • Fibronectins
  • Membrane Glycoproteins
  • Peptide Fragments
  • N-Glycosyl Hydrolases
  • ADP-ribosyl Cyclase
  • CD38 protein, human
  • Cd38 protein, mouse
  • ADP-ribosyl Cyclase 1