Hematopoietic potential and retroviral transduction of CD34+ Thy-1+ peripheral blood stem cells from asymptomatic human immunodeficiency virus type-1-infected individuals mobilized with granulocyte colony-stimulating factor

Blood. 1997 Jun 15;89(12):4299-306.

Abstract

The potential of hematopoietic stem cells (HSCs) from human immunodeficiency virus type-1 (HIV-1)-infected individuals, eg, self-renewal and multilineage differentiative capacity, might be perturbed due to the underlying disease. In this study, we assessed the HSC activity in the CD34+ Thy-1+ cell population of peripheral blood stem cells (PBSCs) of three asymptomatic HIV-1-infected individuals after granulocyte colony-stimulating factor (G-CSF; 10 microg/kg/d) mobilization. On day 4 of G-CSF treatment, 0.8% to 1% of the total blood mononuclear cells were CD34+. Leukapheresis followed by a two-step cell isolation process yielded a CD34+ Thy-1+ cell population of high purity (76% to 92% CD34+ Thy-1+ cells). This cell population showed no evidence of HIV-1-containing cells based on a semiquantitative HIV-1 DNA polymerase chain reaction. Furthermore, the purified cells showed normal hematopoietic potential in in vitro clonogenic assays. Successful gene transfer into committed progenitor cells (colony-forming units-cells) and more primitive stem/progenitor cells (long-term culture colony-forming cells) could be shown after amphotropic retroviral transduction. These data provide evidence that the CD34+ Thy-1+ stem cell compartment can be mobilized and enriched in early stage HIV-1-infected patients. Furthermore, successful transduction of this cell population as a prerequisite for stem cell-based clinical gene therapy protocols was demonstrated.

MeSH terms

  • Adult
  • Antigens, CD34 / analysis
  • Blood Cell Count
  • Cell Separation
  • DNA, Viral / blood
  • Feasibility Studies
  • Female
  • Flow Cytometry
  • Genetic Vectors
  • Granulocyte Colony-Stimulating Factor / pharmacology*
  • HIV Core Protein p24 / blood
  • HIV Infections / blood*
  • Hematopoiesis / drug effects*
  • Hematopoietic Stem Cell Transplantation
  • Hematopoietic Stem Cells / drug effects*
  • Hematopoietic Stem Cells / virology
  • Humans
  • Leukapheresis
  • Male
  • Middle Aged
  • Polymerase Chain Reaction
  • Retroviridae / genetics*
  • Thy-1 Antigens / analysis
  • Viremia / blood

Substances

  • Antigens, CD34
  • DNA, Viral
  • HIV Core Protein p24
  • Thy-1 Antigens
  • Granulocyte Colony-Stimulating Factor