Retroviral transduction of quiescent haematopoietic cells using a packaging cell line expressing the membrane-bound form of stem cell factor

Abstract

Gene therapy vectors based on murine retroviruses are strated that these cells, though quiescent, can still be sucunable to transduce non-dividing cells. This has proven a cessfully transduced. This approach was extended to tarparticular problem in the haematopoietic system where the geting of umbilical cord blood CD34 + cells, a predominantly target cells of choice, the pluripotent stem cells are quiescquiescent population that normally require the addition of ent. In an attempt to circumvent this difficulty we have concytokines for efficient transduction. Using the SCFstructed a retroviral producer line that expresses the memexpressing producer line in the absence of exogenously brane bound form of human recombinant stem cell factor added cytokines, we observed a marked stimulation in (SCF) on its cell surface. This should enable the retroviral transduction efficiency over that achieved using the parent producers to deliver a growth signal to the target cells simproducer line alone. Colonies derived from these cells arisultaneous with their exposure to retrovirus. We tested the ing in semi-solid media were also shown to be positive for ability of these modified producers to transduce a growth expression of a retrovirally encoded reporter gene. factor-starved, SCF-dependent cell line (TF-1) and demon-

Retrovirus-mediated multidrug resistance gene (MDR1) overexpression inhibits chemotherapy-induced toxicity of granulosa cells

“…(15, 16, 21, 22) Here, we examine the potential role of MDR1 as a chemoprotective agent in normal granulosa cells. We show that upregulation of MDR1 in granulosa cells prior to chemotherapy protects from chemotherapy toxicity without adversely affecting the expression of steroidogenic enzymes.…”