The role of surface modification on the culture and transduction of hematopoietic cells for gene therapy

摘要

The ability to inser a tene of interest into pluripotent hematopoietic stem cell has the potential to provide permanent correction for human genetic disorders. Several clinical trials have been performed using genetically modified hematopoietic cells for gene marking (Deisseroth, 1994) or for the treatment of a genetic disorders cells (Kohn, 1995). These studies have found that very low levels of gene transfer are observed in vivo. It has been recognized that the hematopoietic microenvironment is important in hematopoiesis (Klein, 1995). The role of the hematopoietic microenvironment can be divided into three different factors: soluble factors,extracellular matrix molecules, and geometry. The role of soluble factors has been studied extensively. The Dexter culture system (Dexter, 1973), illustrated the need for stromal or accessory cells present in the bone marrow sinuses for ex vivo culture. These studies and others led to the purification, clning and sequencing of recmbinant factors including, granulocyte-colon stimlating factor (G-CSF), which has been approved for clinical use.