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
U Junker, JJ Moon, CS Kalfoglou, I Sniecinski, SJ Forman, JA Zaia, H Kaneshima and E Bohnlein
Progenesys Program, Systemix Inc, Palo Alto, CA 94304, USA.
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.
Volume 89,
Issue 12,
pp. 4299-4306,
06/15/1997
Copyright © 1997 by The American Society of Hematology
