Molecular control of cell cycle progression in primary human hematopoietic stem cells: methods to increase levels of retroviral-mediated transduction.

ABSTRACT

Pluripotent hematopoietic stem cells (HSC) are the ideal targets for gene transfer because they can repopulate a sublethally irradiated recipient, giving rise to all lineages of blood cells. Thus, introduction of a corrected gene into HSC (stem cell gene therapy) should ensure persistent transmission of the gene. To date, the most efficient mode of gene delivery is via Moloney murine leukemia virus (MoMuLV)-based retroviral vectors which stably integrate into the genome of the target cell. The quiescent nature of HSC and the fact that MoMuLV-based retroviral vectors can only integrate into dividing cells are major obstacles in gene therapy. While increasing efforts have been directed toward identifying growth factors which facilitate division of primary hematopoietic progenitor and stem cells, little is known about the molecular mechanisms which these cells use to enter cell cycle. In this review, we will discuss the correlation between the hematopoietic inhibitory and growth factors and their impact on the regulation of the cell cycle components.