LONG-TERM CONTRIBUTION TO THE MYELOID COMPARTMENT BY LINEAGE-COMMITTED STEM-CELLS

The current paradigm concerning the kinetics of hematopoiesis is that only the most primitive pluripotential bone marrow stem cells can supp ort prolonged hematopoiesis whereas more differentiated, lineage-commi tted stem cells can only contribute to a particular lineage for a limi ted period of time. In this study, we present evidence that in mice, t he spleen contains a long-lived myeloid-committed stem cell population (s) that continuously replenishes the mature myeloid lineage for at le ast 9 months. After myeloid-specific retroviral-mediated gene transfer , the exogenous gene could be detected in thioglycollate-induced macro phages and granulocytes by Southern blot analysis and by in situ polym erase chain reaction on an individual cell basis. The targeted stem ce ll population does not repopulate the bone marrow in secondary recipie nts and did not give rise to cells other than cells of the myeloid lin eage, It therefore represents the first nonpluripotential stem cell po pulation capable of replenishing a hemopoietic lineage for a long peri od of time. The ability to target a myeloid-specific stem cell could f acilitate gene therapy of congenital disorders of the myeloid system s uch as lysosomal storage diseases. It also offers a unique opportunity to assess the immunologic consequences of expressing an exogenous gen e of choice exclusively in the myeloid lineage. (C) 1998 by The Americ an Society of Hematology.