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Negatively Modulates Self-Renewal of Repopulating Human Hemopoietic Stem Cells1
Hemopoietic Stem Cell Laboratory, Lund Strategic Research Center for Stem Cell Biology and Cell Therapy, Lund University, Lund, Sweden
Whereas multiple growth-promoting cytokines have been demonstrated to be involved in regulation of the hemopoietic stem cell (HSC) pool, the potential role of negative regulators is less clear. However, IFN-
, if overexpressed, can mediate bone marrow suppression and has been directly implicated in a number of bone marrow failure syndromes, including graft-vs-host disease. Whether IFN- might directly affect the function of repopulating HSCs has, however, not been investigated. In the present study, we used in vitro conditions promoting self-renewing divisions of human HSCs to investigate the effect of IFN- on HSC maintenance and function. Although purified cord blood CD34+CD38– cells underwent cell divisions in the presence of IFN-, cycling HSCs exposed to IFN- in vitro were severely compromised in their ability to reconstitute long-term cultures in vitro and multilineage engraft NOD-SCID mice in vivo (>90% reduced activity in both HSC assays). In vitro studies suggested that IFN- accelerated differentiation of targeted human stem and progenitor cells. These results demonstrate that IFN- can negatively affect human HSC self-renewal.
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