Hematopoietic stem cell expansion and gene therapy

Abstract

Hematopoietic stem cell (HSC) gene therapy remains a highly attractive treatment option for many disorders, including hematologic conditions, immunodeficiencies including human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS), and other genetic disorders such as lysosomal storage diseases. In this review, we discuss the successes, side-effects and limitations of current gene therapy protocols. In addition, we describe the opportunities presented by implementing ex vivo expansion of gene-modified HSC, as well as summarize the most promising ex vivo expansion techniques currently available. We conclude by discussing how some of the current limitations of HSC gene therapy could be overcome by combining novel HSC expansion strategies with gene therapy.

Figure 1. Schematic representation of ex vivo expansion of gene-modified cells in a nonhuman primate model

Bone marrow, peripheral blood, or cord blood hematopoietic stem cells (HSCs) are removed from the monkey for ex vivo manipulation. Cells are gene-modified in vitro and expanded. Prior to infusion, a sample of the cells is tested to determine efficiency of gene correction and safety of the integration site profile. If cells pass this quality-control checkpoint, they are transplanted back into the non-myeloablated monkey.