Repopulation defect of stem hemopoietic cells after retroviral transduction of a foreign gene

It is demonstrated that the proliferative potential of mouse hemopoietic stem cells does not decrease after insertion of foreign DNA and does not depend on the number of inserted DNA copies. However, transduced cells develop a repopulation defect manifesting itself as a reduced production of splenic colony-forming units in restored mice. The mice restored with transduced cells more rapidly reverse to the recipient hemopoiesis. This defect is associated with the induction of proliferation of stem hemopoietic cells by high concentration of cytokines but not with integration of the foreign gene. The repopulation defect is less pronounced in mice restored with cells stimulated for gene transduction by culturing on irradiated sublayer of long-term bone marrow cells without exogenous cytokines.[PUBLICATION ABSTRACT]